下面介绍参考例和实施例,但不限制本发明。
括号中的溶剂给出显影或洗脱溶剂,在色谱分离和TLC中使用的溶剂 的比例按体积计。
NMR数据与测量中使用的溶剂(在括号中的)一起给出。
参考例1
2-甲基-4-甲氧基苯基乙腈
在氩气气氛下,将N-溴丁二酰亚胺(17.8g)和2,2’-偶氮二异丁腈(492mg) 加入1,2-二甲基-4-甲氧基苯(13.6g)在四氯化碳(200ml)中的溶液。将该混合 物再回流6.5小时。将该反应混合物用冰浴冷却。过滤除去不溶物质,并用 四氯化碳洗涤。将合并的滤液浓缩。将残余物溶解入N,N-二甲基甲酰胺 (100ml)中,并将氰化钠(9.86g)加入该混合物中。将该混合物在室温下搅拌 过夜。将该反应混合物倒入水中,并将该混合物用乙醚洗涤。将有机层用 氯化钠饱和水溶液洗涤,在无水
硫酸镁上干燥并浓缩。将残余物通过硅胶 柱色谱(乙酸乙酯∶正己烷=1∶6→1∶4)纯化,得到标题化合物(11.78g),它具有 如下物理数据:
TLC:Rf0.20(正己烷∶乙酸乙酯=9∶1);
NMR(300MHz,CDCl3):δ7.24(d,J=8.0Hz,1H),6.78-6.72(m,2H),3.79(s, 3H),3.60(s,2H),2.32(s,3H)。
参考例2
1-氰基-1-(2-甲基-4-甲氧基苯基)丙-2-酮
在氩气气氛下,将金属钠(2.3g)分数次加入参考例1中制备的化合物 (11.7g)在乙酸乙酯(60ml)中的溶液中。将该混合物在50℃下搅拌2小时。 将乙酸乙酯(40ml)加入反应混合物中,并将该混合物回流2.5小时,然后将 其在室温下搅拌过夜。过滤收集沉淀物,并用乙醚洗涤。将获得的晶体溶 于水(300ml)中。将该溶液通过加入2N乙酸调节pH4,并用乙酸乙酯萃取。 将有机层在硫酸钠上干燥,得到标题化合物(12.06g),它具有如下物理数据 TLC:Rf0.45(正己烷∶乙酸乙酯=1∶1)。
参考例3
2-氯-4-甲氧基硼酸
将3-氯-4-溴苯甲醚(2.14g)在无水四氢呋喃(10ml)中的溶液在-78℃下冷 却。将1.56M正丁基锂/己烷(6.5ml)滴加入该溶液中,并将该混合物搅拌30 分钟。将硼酸三异丙基酯(2.3ml)滴加入该反应混合物中,并将该混合物在- 78℃下搅拌2小时。将
氯化铵的饱和水溶液加入反应混合物中,并将该混 合物用乙酸乙酯萃取,将有机层用氯化钠饱和水溶液洗涤,在无水硫酸钠 上干燥并浓缩。将获得的固体用叔丁基甲基醚(4ml)洗涤,过滤并干燥,得 到标题化合物(681mg),它具有如下物理数据:
TLC:Rf0.55(二氯甲烷∶甲醇=19∶1);
NMR(300MHz,CDCl3):δ7.22(d,J=8.4Hz,1H),6.93(d,J=2.4Hz,1H), 6.86(dd,J=8.4,2.4Hz,1H),3.79(s,3H)。
参考例4
4-(2-氯-4-甲氧基苯基)-5-甲基异噁唑
将四(三苯基膦)钯(36mg)加入参考例3中制备的化合物(644mg),4-碘- 5-甲基异噁唑(658mg)和
碳酸氢钠(791mg)在二甲氧基乙烷(2.5ml)/水(2.5ml) 中的悬浮液中。将该混合物在80℃下搅拌16小时。向冷却至室温的反应混 合物中,加入水和乙酸乙酯。过滤除去不溶物质。从滤液中分离有机层, 将其用氯化钠的饱和水溶液洗涤,在无水硫酸钠上干燥并浓缩。将残余物 在硅胶柱色谱(正己烷∶乙酸乙酯=19∶1→15∶1)上纯化,得到标题化合物 (637mg),它具有如下物理数据:
TLC:Rf0.44(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.29(brs,1H),7.16(d,J=8.4Hz,1H),7.04(d, J=2.4Hz,1H),6.87(dd,J=8.4,2.4Hz,1H),3.84(s,3H),2.41(brs,3H)。
参考例5
1-氰基-1-(2-氯-4-甲氧基苯基)丙-2-酮
将1.5M甲醇钠/甲醇(2.8ml)加入参考例4中制备的化合物(623mg)在甲 醇(2.8ml)中的溶液中,并将该混合物搅拌4小时。将该反应混合物用水稀 释,并用己烷/叔丁基甲基醚(10ml;1∶1)洗涤。将水层通过加入4N乙酸(1ml) 调节pH5,并用乙酸乙酯萃取。将有机层用饱和碳酸氢钠水溶液和饱和氯 化钠水溶液洗涤,在无水硫酸镁上干燥并浓缩得到标题化合物(497mg),它 具有如下物理数据:
TLC:Rf0.13(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.38(d,J=8.4Hz,1H),7.00(d,J=2.4Hz,1H), 6.89(dd,J=8.4,2.4Hz,1H),5.11(s,1H),3.83(s,3H),2.29(s,3H)。
参考例6
5-氨基-3-甲基-4-(2-甲基-4-甲氧基苯基)吡唑
将乙酸(8.0ml)和肼一水合物(4.5ml)加入参考例2中制备的化合物在甲 苯(200ml)中的溶液中。将该混合物回流5.5小时并在室温下搅拌过夜。将 该反应混合物浓缩。将6N乙酸w加入残余物中,并将该溶液用乙酸乙酯/ 正己烷(30ml/30ml)萃取。将水层通过加入浓
氨水碱化。将有机层在无水硫 酸镁上干燥,并浓缩得到标题化合物(8.38g),它具有如下物理数据:
TLC:Rf0.30(氯仿∶甲醇=9∶1);
NMR(300MHz,CDCl3):δ7.08(d,J=8.0Hz,1H),6.84(d,J=2.5Hz,1H), 6.77(dd,J=8.0,2.5Hz,1H),4.10(brs,3H),3.83(s,3H),2.18(s,3H),2.07(s,3H)。
实施例1
8-羟基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
将环戊酮-2-羧酸乙酯(0.40ml)加入参考例6中制备的化合物(500mg)在 乙酸(3ml)中的溶液中,并将该混合物回流3小时。将该反应混合物冷却至 室温后,将乙醚/正己烷(10ml;2∶1)加入该混合物中。过滤收集沉淀物,并 将晶体用乙醚正己烷(10ml;2∶1)洗涤,干燥,得到标题化合物(480mg),它 具有如下物理数据:
TLC:Rf0.47(氯仿∶甲醇=9∶1);
NMR(300MHz,DMSO-d6):δ11.90(brs,1H),7.10(d,J=8.0Hz,1H),6.93(d, J=3.0Hz,1H),6.83(dd,J=8.0,3.0Hz,1H),3.78(s,3H),2.81(t,J=7.5Hz,2H), 2.66(t,J=7.5Hz,2H),2.07(s,3H),2.05(s,3H),2.03(m,2H)。
参考例7
8-氯-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
将磷酰氯(0.60ml)和二乙基苯胺(0.25ml)加入实施例1中制备的化合物 (400mg)在甲苯(4ml)中的悬浮液中。将该混合物回流1小时。将反应混合物 冷却,将其倒入碳酸氢钠的
冷却水溶液中。将该混合物搅拌10分钟以使过 量的磷酰氯降解。将反应混合物用乙酸乙酯萃取。将有机层用饱和氯化钠 水溶液洗涤,在无水硫酸镁上干燥并浓缩。将残余物在硅胶柱色谱(乙酸乙 酯∶正己烷=1∶3→1∶2)上纯化,得到标题化合物(411mg),它具有如下物理数 据:
TLC:Rf0.52(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.5Hz,1H),6.88(d,J=2.5Hz,1H), 6.81(dd,J=8.5,2.5Hz,1H),3.83(s,3H),3.09-3.00(m,4H),2.40(s,3H),2.23(m, 2H),2.15(s,3H)。
实施例2
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
将参考例7中制备的化合物(150mg)与3-戊胺的混合物在140℃下搅拌 1小时。将该反应混合物冷却,并在硅胶柱色谱(乙酸乙酯∶正己烷=1∶3)上纯 化,得到标题化合物(169mg),它具有如下物理数据:
TLC:Rf0.57(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.5Hz,1H),6.85(d,J=3.0Hz,1H), 6.78(dd,J=8.5,3.0Hz,1H),6.21(d,J=10.5Hz,1H),3.82(s,3H),3.81(m,1H), 3.08(t,J=7.0Hz,2H),2.89(t,J=8.0Hz,2H),2.30(s,3H),2.19(s,3H),2.14(m,2H), 1.69(m 4H),1.02(m,6H)。
实施例2(1)-2(365)
如下化合物通过下面的方法获得:用相应的化合物代替1,2-二甲基-4- 甲氧基苯,借助与参考例1→参考例2→参考例6→实施例1反应系列相同 工艺,用相应的化合物代替环戊酮-2-羧酸乙酯→参考例7→实施例2,用相 应的化合物代替3-戊胺,或用参考例5中制备的化合物或相应的化合物, 借助与参考例6→实施例1→参考例7→实施例2反应系列相同的工艺,或 随后借助已知的形成化合物的盐的方法。
实施例2(1)
8-(N-乙基-N-正-丁氨基)-2-甲氧基甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.43(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.22(d,J=8.7Hz,1H),6.84(d,J=2.7Hz,1H), 6.77(dd,J=8.7,2.7Hz,1H),4.49(m,2H),3.81(s,3H),3.67(q,J=7.2Hz,2H), 3.61(t,J=7.2Hz,2H),3.33(s,3H),2.97(t,J=7.2Hz,2H),2.91(t,J=7.8Hz,2H), 2.19(s,3H),2.13(m,2H),1.55(m,2H),1.35(m,2H),1.17(t,J=7.2Hz,3H), 0.89(t,J=7.2Hz,3H)。
实施例2(2)
8-(N-丙基-N-(2-羟乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.80(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),3.90(t,J=4.8Hz,2H),3.83(s,3H),3.64(m,2H), 3.43(m,2H),2.98(t,J=7.2Hz,2H),2.92(t,J=7.8Hz,2H),2.31(s,3H),2.17(s,3 H),2.15(m,2H),1.58(m,2H),0.95(t,J=7.2Hz,3H)。
实施例2(3)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-噻酚并[3,4-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.51(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.5Hz,1H),6.86(d,J=2.5Hz,1H), 6.79(dd,J=8.5,2.5Hz,1H),6.44(d,J=10.0Hz,1H),4.32(brs,2H),4.14(brs,2H), 3.82(s,3H),3.76(m,1H),2.32(s,3H),2.18(s,3H),1.84-1.57(m 4H),1.03(t, J=7.0Hz,6H)。
实施例2(4)
9-(3-戊氨基)-6-甲基-5-(2-甲基-4-甲氧基苯基)-2,3-二氢-噻酚并[3,2-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.40(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.5Hz,1H),6.85(d,J=3.0Hz,1H), 6.79(dd,J=8.5,3.0Hz,1H),6.17(d,J=10.0Hz,1H),3.99(m,1H),3.82(s,3H), 3.36-3.20(m,4H),2.30(s,3H),2.18(s,3H),1.82-1.56(m 4H),1.03(t,J=7.5Hz, 6H)。
实施例2(5)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.33(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.5Hz,1H),6.86(d,J=2.5Hz,1H), 6.79(dd,J=8.5,2.5Hz,1H),6.32(d,J=10.0Hz,1H),5.29(s,2H),4.90(brs,2H), 3.82(s,3H),3.24(m,1H),2.33(s,3H),2.18(s,3H),1.84-1.56(m 4H),1.02(t, J=7.5Hz,6H)。
实施例2(6)
9-(3-戊氨基)-6-甲基-5-(2-甲基-4-甲氧基苯基)-2,3-二氢-呋喃并[3,2-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.43(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(brs,1H),7.12(d,J=8.4Hz,1H),6.89(d, J=2.7Hz,1H),6.82(dd,J=8.4,2.7Hz,1H),4.76(t,J=9.0Hz,2H),4.30(m,1H), 3.83(s,3H),3.74(t,J=9.0Hz,2H),2.34(s,3H),2.19(s,3H),1.90-1.70(m,4H), 1.04(m,6H)。
实施例2(7)
9-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,6,7,8-四氢-吡唑并[3,2-b] 喹唑啉盐酸
TLC:Rf0.45(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ13.04(brs,1H),7.91(brs,1H),7.15(d,J=8.5Hz, 1H),6.96(d,J=2.5Hz,1H),6.87(dd,J=8.5,2.5Hz,1H),5.65(brs,1H),3.79(s,3H), 2.75(m,2H),2.58(m,2H),2.19(s,3H),2.05(s,3H),1.88-1.64(m,8H),0.91(t, J=7.5Hz,6H)。
实施例2(8)
6-甲基-5-(2-甲基-4-甲氧基苯基)-9-[(2S,4R)-4-甲氧基-2-甲氧基甲基吡咯 烷-1-基]-2,3-二氢-呋[3,2-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.24(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,DMSO-d6):δ7.09(d,J=7.5Hz,1H),6.90(d,J=2.4Hz,1H), 6.81(dd,J=7.5,2.4Hz,1H),5.07(brs,1H),4.66(dt,J=9.0,9.0Hz,1H),4.56(dt, J=9.0,9.0Hz,1H),4.24(dd,J=12.6,3.6Hz,1H),4.05(brs,1H),3.85(d,J=12.6Hz, 1H),3.77(s,3H),3.42(dd,J=10.2,3.9Hz,1H),3.33(dd,J=10.2,5.1Hz,1H), 3.22(dd,J=9.0,9.0Hz,2H),3.21(s,3H),3.18(s,3H),2.18(s,3H),2.07(s,3H), 2.30-1.95(m,2H)。
实施例2(9)
9-(3-戊氨基)-6-甲基-5-(2-甲基-4-甲氧基苯基)-2,3-二氢-吡咯并[3,2-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.37(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=2.7,8.4Hz,1H),5.86(d,J=10.5Hz,1H),4.07(m,1H),3.82(s,3H), 3.58(t,J=8.1Hz,2H),3.06(t,J=8.1Hz,2H),2.30(s,3H),2.19(s,3H),1.52-1.82(m, 4H),1.01(m,6H)。
实施例2(10)
2-甲基-3-(2-甲基-4-甲氧基苯基)-8-[(2S,4R)-4-甲氧基-2-甲氧基甲基吡咯 烷-1-基]-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.30(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.15 and 7.07(d,J=8.4Hz,两个构象异构体, 1H),6.89 and 6.87(d,J=2.7Hz,两个构象异构体,1H),6.83 and 6.80(dd,J=8.4, 2.7Hz,两个构象异构体,1H),5.65(brs,1H),4.32-4.10(m,3H),3.82(s,3H), 3.50-3.40(m,4H),3.367 and 3.361(s,两个构象异构体,3H),3.29 and 3.28(s, 两个构象异构体,3H),3.23-2.99(m,2H),2.42(m,1H),2.30-2.10(m,3H),2.245 and 2.240(s,两个构象异构体,3H),2.22 and 2.14(s,两个构象异构体,3H).
实施例2(11)
2-甲基-3-(2-甲基-4-甲氧基苯基)-8-[(2S,4R)-4-甲氧基-2-甲氧基甲基吡 咯烷-1-基]-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]
嘧啶盐酸
TLC:Rf0.22(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,DMSO-d6)7.10(brs,1H),6.89(d,J=2.4Hz,1H),6.81(dd, J=8.1,2.4Hz,1H),5.33(d,J=10.8Hz,1H),5.25(brs,1H),5.15(d,J=10.8Hz,1H), 4.85(d,J=14.4Hz,1H),4.75(d,J=14.4Hz,1H),4.10-3.85(m,3H),3.77(s,3H), 3.39(dd,J=9.9,4.5Hz,1H),3.28(dd,J=9.9,5.1Hz,1H),3.22(s,3H),3.15(s,3H), 2.25(m,1H),2.21(s,3H),2.15-2.00(m,4H).
实施例2(12)
6-甲基-5-(2-甲基-4-甲氧基苯基)-9-[(2S,4R)-4-甲氧基-2-甲氧基甲基吡 咯烷-1-基]-2,3-二氢-吡咯并[3,2-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.43(氯仿∶甲醇=20∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=2.7,8.4Hz,1H),4.71(m,1H),4.20(m,1H),4.06(m,1H),3.82(s,3H), 3.60(t,J=7.8Hz,2H),3.54(m,1H),3.48(dd,J=4.5,9.6Hz,1H),3.39(m,1H), 3.34(s,3H),3.28(s,3H),3.09(m,2H),2.24-2.40(m,4H),2.18(s,3H),2.01(m, 1H).
实施例2(13)
8-异丙氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.34(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),6.39(d,J=9.6Hz,1H),5.32(s,2H),4.90(s,2H),3.82(s, 3H),3.74(m,1H),2.32(s,3H),2.16(s,3H),1.41(d,J=6.6Hz,6H).
实施例2(14)
8-[(2S)-1,1-二甲氧基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.26(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.86(d,J=2.4Hz,1H), 6.79(dd,J=8.1,2.4Hz,1H),6.57(brd,J=11.1Hz,1H),5.36(d,J=9.9Hz,1H), 5.26(d,J=9.9Hz,1H),4.90(s,2H),4.33(d,J=3.9Hz,1H),3.82(s,3H),3.50(s,3H), 3.48(s,3H),3.39(m,1H),2.32(s,3H),2.17(s,3H),1.88(m,1H),1.68(m,1H), 1.04(brs,3H).
实施例2(15)
8-[(2S)-1,1-二甲氧基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.30(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.85(d,J=3.0Hz,1H), 6.77(dd,J=8.1,3.0Hz,1H),6.47(brd,J=11.8Hz,1H),4.34(brs,1H),4.01(m,1H), 3.81(s,3H),3.49(s,6H),3.19-3.00(m,2H),2.89(t,J=7.8Hz,2H),2.30(s,3H), 2.18(s,3H),2.13(m,2H),1.86(m,1H),1.65(m,1H),1.04(brs,3H).
实施例2(16)
8-(1,3-二甲氧基丙-2-基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.42(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.87(brd,J=8.1Hz,1H), 6.85(d,J=2.4Hz,1H),6.79(dd,J=8.1,2.4Hz,1H),5.33(s,2H),4.89(s,2H),3.81(s, 3H),3.75(m,1H),3.62(d,J=4.8Hz,4H),3.42(s,6H),2.33(s,3H),2.16(s,3H).
实施例2(17)
8-双(2-甲氧基乙基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.24(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.87(d,J=2.7Hz,1H), 6.79(dd,J=8.1,2.7Hz,1H),5.22(s,2H),4.89(s,2H),3.88(t,J=6.0Hz,4H),3.82(s, 3H),3.55(t,J=6.0Hz,4H),3.30(s,6H),2.33(s,3H),2.16(s,3H).
实施例2(18)
8-(1,3-二甲氧基丙-2-基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.53(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.01(d,J=8.4Hz,1H),6.72(d,J=2.7Hz,1H), 6.64(dd,J=8.4,2.7Hz,1H),6.60(d,J=9.9Hz,1H),4.14(m,1H),3.69(s,3H), 3.50(d,J=5.4Hz,4H),3.30(s,6H),2.99(t,J=7.2Hz,2H),2.76(t,J=7.8Hz,2H), 2.18(s,3H),2.04(s,3H),2.01(m,2H).
实施例2(19)
8-双(2-甲氧基乙基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.41(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.78(dd,J=8.4,2.7Hz,1H),3.88(t,J=5.7Hz,4H),3.82(s,3H),3.52(t,J=5.7Hz, 4H),3.30(s,6H),3.00(t,J=6.9Hz,2H),2.91(t,J=7.8Hz,2H),2.32(s,3H),2.18(s, 3H),2.14(m,2H).
实施例2(20)
(5RS)-8-(3-戊氨基)-2,5-二甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.44(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,DMSO-d6):δ8.71(brs,1H),7.15(d,J=8.5Hz,1H),6.93(d, J=2.5Hz,1H),6.85(dd,J=8.5,2.5Hz,1H),5.70(brs,1H),5.25(dd,J=10.0,2.0Hz, 1H),5.17(d,J=10.0Hz,1H),5.11(m,1H),3.79(s,3H),3.26(m,1H),2.26(s,3H), 2.10(s,3H),1.83-1.57(m 4H),1.41(d,J=5.5Hz,3H),0.93-0.83(m,6H).
实施例2(21)
8-(3-戊氨基)-2-甲基-3-(2,4-二氯苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶
TLC:Rf0.50(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.50(d,J=2.0Hz,1H),7.35(d,J=8.5Hz,1H), 7.29(dd,J=8.5,2.0Hz,1H),6.23(d,J=10.5Hz,1H),3.81(m,1H),3.09(t,J=7.5Hz, 2H),2.91(t,J=7.5Hz,2H),2.34(s,3H),2.15(m,2H),1.82-1.55(m 4H),1.01(t, J=7.5Hz,6H).
实施例2(22)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-吡咯并[3,4-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.48(氯仿∶甲醇=10∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1H,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=2.7,8.1Hz,1H),6.29(d,J=10.2Hz,1H),4.43(s,2H),4.10(s,2H), 3.82(s,3H),3.49(m,1H),2.32(s,3H),2.18(s,3H),1.55-1.84(m,4H),1.02(m, 6H).
实施例2(23)
8-二乙基氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.67(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),3.82(s,3H),3.66(q,J=7.2Hz,4H),2.99(t,J=7.5Hz, 2H),2.91(t,J=7.5Hz,2H),2.33(s,3H),2.19(s,3H),2.13(m,2H),1.18(t,J=7.2Hz, 6H).
实施例2(24)
8-(N-乙基-N-正-丁氨基)-2-甲基-3-(2,4-二氯苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.78(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.17(d,J=8.4Hz,1H),6.86(d,J=3.0Hz,1H), 6.79(dd,J=8.4,3.0Hz,1H),3.82(s,3H),3.70-3.56(m,4H),2.97(t,J=6.9Hz,2H), 2.91(t,J=7.7Hz,2H),2.33(s,3H),2.19(s,3H),2.13(m,2H),1.55(m,2H),1.32(m, 2H),1.17(t,J=7.2Hz,3H),0.90(t,J=7.2Hz,3H).
实施例2(25)
8-二环丙基甲基氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.40(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=8.1,2.7Hz,1H),6.36(d,J=10.2Hz,1H),3.82(s,3H),3.41(m,1H), 3.01(t,J=7.2Hz,2H),2.87(t,J=8.1Hz,2H),2.31(s,3H),2.19(s,3H),2.10(m,2H), 1.20-1.08(m,2H),0.66-0.32(m,8H).
实施例2(26)
8-(N-丙基-N-(2-羟乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.26(正己烷∶乙酸乙酯=1∶2);
NMR(300MHz,CDCl3):δ7.14(d,J=8.4Hz,1H),6.87(d,J=2.7Hz,1H), 6.80(dd,J=8.4,2.7Hz,1H),6.54(brs,1H),5.21(s,2H),4.89(s,2H),3.96(brt, J=4.8Hz,2H),3.83(s,3H),3.80(m,2H),3.29(t,J=7.5Hz,2H),2.33(s,3H), 2.17(s,3H),1.63(m,2H),1.00(t,J=7.5Hz,3H).
实施例2(27)
8-(3-戊氨基)-2-甲氧基甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.27(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.19(d,J=8.5Hz,1H),6.85(d,J=2.5Hz,1H), 6.78(dd,J=8.5,2.5Hz,1H),6.32(d,J=10.5Hz,1H),4.54-4.40(m,2H),3.82(s,3H), 3.81(m,1H),3.37(s,3H),3.10(t,J=7.0Hz,2H),2.91(t,J=8.0Hz,2H),2.20(s,3H), 2.14(m,2H),1.80-1.53(m,4H),1.08-0.94(m,6H).
实施例2(28)
8-(3-戊氨基)-2-甲基-3-(1,3-二氧杂茚满-5-基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.61(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.22(d,J=1.5Hz,1H),7.10(dd,J=1.5,8.1Hz, 1H),6.89(d,J=8.1Hz,1H),6.20(br d,J=10.5Hz,1H),5.96(s,2H),3.80(m,1H), 3.08(t,J=7.5Hz,2H),2.94(t,J=8.1Hz,2H),2.52(s,3H),2.15(m,2H),1.51- 1.80(m,4H),1.00(t,J=7.5Hz,6H).
实施例2(29)
8-(3-戊氨基)-2-甲基-3-(3,4-二甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.56(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=2.1Hz,1H),7.19(dd,J=2.1,8.1Hz, 1H),6.96(d,J=8.1Hz,1H),6.20(br d,J=10.5Hz,1H),3.93(s,3H),3.91(s,3H), 3.80(m,1H),3.09(t,J=7.2Hz,2H),2.94(t,J=7.5Hz,2H),2.55(s,3H),2.16(m,2H), 1.53-1.81(m,4H),1.00(t,J=7.2Hz,6H).
实施例2(30)
8-环丙基氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.33(正己烷∶乙酸乙酯=3∶2);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.1,2.7Hz,1H),6.62(brs,1H),5.54(brs,2H),4.91(brs,2H),3.82(s, 3H),2.89(m,1H),2.30(s,3H),2.15(s,3H),0.98-0.84(m,4H).
实施例2(31)
8-(3-戊氨基)-2-环丁基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.62(苯∶乙酸乙酯=5∶1);
NMR(300MHz,CDCl3):δ7.09(d,J=8.1Hz,1H),6.83(d,J=2.7Hz,1H), 6.75(dd,J=8.1,2.7Hz,1H),6.35(d,J=10.5Hz,1H),3.82(s,3H),3.81(m,1H), 3.53(m,1H),3.08(t,J=7.5Hz,2H),2.88(t,J=7.8Hz,2H),2.41(m,2H),2.28- 2.06(m,4H),2.15(s,3H),2.01-1.58(m,6H),1.05(t,J=7.5Hz,3H),1.02(t, J=7.8Hz,3H).
实施例2(32)
8-(3-戊氨基)-2-乙基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.59(苯∶乙酸乙酯=5∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.85(d,J=2.7Hz,1H), 6.77(dd,J=8.1,2.7Hz,1H),6.27(d,J=10.5Hz,1H),3.82(s,3H),3.80(m,1H), 3.08(t,J=7.5Hz,2H),2.89(t,J=7.8Hz,2H),2.67(m,2H),2.17(s,3H),2.13(m, 2H),1.81-1.52(m,4H),1.16(t,J=7.2Hz,3H),1.04(t,J=7.5Hz,3H),1.01(t, J=7.8Hz,3H).
实施例2(33)
8-(3-戊氨基)-2-异丙基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.60(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.28(m,1H),7.09(d,J=8.4Hz,1H),6.90(d, J=2.4Hz,1H),6.81(dd,J=8.4,2.4Hz,1H),3.99(m,1H),3.84(s,3H),3.49(m,2H), 3.12(t,J=7.2Hz,2H),2.99(m,1H),2.28(m,2H),2.20(s,3H),1.85(m,2H), 1.74(m,2H),1.24(d,J=6.9Hz,3H),1.19(d,J=7.2Hz,3H),1.08(t,J=7.5Hz,3H), 1.06(t,J=7.5Hz,3H).
实施例2(34)
8-(2-乙基丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.55(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.46(m,1H),7.11(d,J=8.4Hz,1H),6.89(d, J=2.4Hz,1H),6.82(dd,J=8.4,2.4Hz,1H),3.83(s,3H),3.74(t,J=6.0Hz,2H), 3.49(t,J=7.8Hz,2H),3.21(t,J=7.5Hz,2H),2.28(s,3H),2.26(m,2H),2.19(s,3H), 1.68(m,1H),1.53(m,4H),1.00(t,J=7.5Hz,6H).
实施例2(35)
8-(3-戊氨基)-2-甲基硫甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.31(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.31(brd,J=10.8Hz,1H),7.16(d,J=8.4Hz,1H), 6.89(d,J=2.4Hz,1H),6.80(dd,J=8.4,2.4Hz,1H),4.00(brs,1H),3.83(s,3H), 3.70(d,J=13.5Hz,1H),3.60(d,J=13.5Hz,1H),3.50(m,2H),3.14(t,J=7.2Hz,2H), 2.29(m,2H),2.32(s,3H),2.04(s,3H),1.95-1.65(m,4H),1.07(t,J=7.2Hz,3H), 1.05(t,J=7.5Hz,3H).
实施例2(36)
8-(N-甲基-N-环丙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.16(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.1,2.7Hz,1H),5.47(brs,2H),4.90(brs,2H),3.82(s,3H),3.45(s,3H), 2.80(m,1H),2.33(s,3H),2.16(s,3H),0.84(d,J=6.0Hz,4H).
实施例2(37)
8-(3-戊氨基)-2-甲基-3-(2,4-二甲苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶
TLC:Rf0.50(苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.13(d,J=7.5Hz,1H),7.11(brs,1H),7.03(m, 1H),6.21(d,J=10.8Hz,1H),3.80(m,1H),3.08(t,J=6.9Hz,2H),2.89(t,J=7.5Hz, 2H),2.34(s,3H),2.31(s,3H),2.18(s,3H),2.13(m,2H),1.56-1.82(m,4H), 1.02(m,6H).
实施例2(38)
8-(3-戊氨基)-2-甲基-3-(2,5-二甲苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a1嘧啶盐酸
TLC:Rf0.54(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.31(br d,J=10.2Hz,1H),7.24(d,J=7.5Hz,1H), 7.15(br dd,J=1.2,7.5Hz,1H),7.01(brs,1H),3.99(m,1H),3.49(t,J=7.5Hz,2H), 3.14(t,J=6.9Hz,2H),2.35(s,3H),2.32(s,3H),2.29(m,2H),2.18(s,3H),1.64- 1.94(m,4H),1.07(t,J=7.5Hz,3H),1.06(t,J=7.2Hz,3H).
实施例2(39)
8-环丁氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.36(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.7Hz,1H),6.85(d,J=2.7Hz,1H), 6.77(dd,J=8.7,2.7Hz,1H),6.50(brd,J=8.4Hz,1H),4.46(m,1H),3.81(s,3H), 3.12(t,J=7.2Hz,2H),2.88(t,J=7.8Hz,2H),2.43(m,2H),2.30(s,3H),2.23- 2.08(m,4H),2.16(s,3H),1.90-1.70(m,2H).
实施例2(40)
8-(N-乙基-N-环丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.38(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.12(d,J=8.7Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=8.7,2.7Hz,1H),4.74(m,1H),3.99(m,2H),3.83(s,3H),3.48(t, J=7.5Hz,2H),2.98(t,J=7.5Hz,2H),2.20-2.10(m,6H),2.30(s,3H),2.17(s,3H), 1.90-1.70(m,2H),1.16(t,J=7.2Hz,3H).
实施例2(41)
8-(丙-1,3-二醇-2-基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.44(氯仿∶甲醇=9∶1);
NMR(300MHz,CDCl3):δ7.17(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.1,2.7Hz,1H),6.73(d,J=10.2Hz,1H),4.12(m,1H),3.98-3.83(m, 4H),3.82(s,3H),3.05(t,J=7.2Hz,2H),2.87(t,J=8.1Hz,2H),2.30(s,3H),2.16(s, 3H),2.11(m,2H).
实施例2(42)
8-(3-戊氨基)-2-(2-呋喃基)-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.33(正己烷∶乙酸乙酯=4∶1);
NMR(300MHz,CDCl3):δ7.47(m,1H),7.21(d,J=8.1Hz,1H),6.87(d, J=2.7Hz,1H),6.81(dd,J=8.1,2.7Hz,1H),6.38-6.30(m,2H),6.05(m,1H),3.84(s, 3H),3.82(m,1H),3.11(t,J=7.2Hz,2H),2.91(t,J=7.8Hz,2H),2.15(m,2H), 2.10(s,3H),1.70(m,4H),1.04(t,J=7.2Hz,3H),1.01(t,J=7.2Hz,3H).
实施例2(43)
8-(3-戊氨基)-2-苯基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.41(正己烷∶乙酸乙酯=4∶1);
NMR(300MHz,CDCl3):δ7.59-7.54(m,2H),7.45-7.19(m,5H),6.88- 6.82(m,2H),4.04(m,1H),3.85(s,3H),3.55(t,J=7.8Hz,2H),3.17(t,J=7.8Hz, 2H),2.32(m,2H),2.05(s,3H),1.97-1.55(m,4H),1.10(t,J=6.9Hz,3H),1.07(t, J=7.2Hz,3H).
实施例2(44)
8-(2-二甲氨基乙基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.30(二氯甲烷∶甲醇=19∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.85(d,J=2.7Hz,1H), 6.77(dd,J=8.4,2.7Hz,1H),6.71(t,J=5.7Hz,1H),3.82(s,3H),3.75(dt,J=5.7, 6.3Hz,2H),3.19(t,J=7.5Hz,2H),2.88(t,J=7.5Hz,2H),2.63(t,J=6.3Hz,2H), 2.33(s,6H),2.31(s,3H),2.17(s,3H),2.12(m,2H).
实施例2(45)
8-(N-甲基-N-(2-二甲氨基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.46(二氯甲烷∶甲醇=9∶1);
NMR(300MHz,吡啶-d50.5m1+CDCl30.1m1):δ7.42(d,J=8.4Hz,1H), 7.04(d,J=2.7Hz,1H),6.96(dd,J=8.4,2.7Hz,1H),4.21(t,J=7.5Hz,2H),3.85(t, J=7.5Hz,2H),3.75(s,3H),3.14(s,3H),3.00(s,6H),2.90(t,J=7.5Hz,2H),2.80(t, J=7.5HZ,2H),2.41(s,3H),2.36(s,3H),1.90(m,2H).
实施例2(46)
8-(N-乙基-N-(2-二甲氨基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.46(二氯甲烷∶甲醇=9∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=8.4,2.7Hz,1H),3.82(s,3H),3.80(t,J=7.2Hz,2H),3.64(q,J=7.2Hz, 2H),2.99(t,J=7.5Hz,2H),2.90(t,J=7.5Hz,2H),2.56(t,J=7.2Hz,2H),2.31(s, 3H),2.25(s,6H),2.17(s,3H),2.12(m,2H),1.17(t,J=7.2Hz,3H).
实施例2(47)
8-(4-庚氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.50(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.27(brd,J=9.6Hz,1H),7.11(d,J=8.4Hz,1H), 6.88(d,J=2.7Hz,1H),6.81(dd,J=8.4,2.7Hz,1H),4.12(m,1H),3.82(s,3H), 3.49(t,J=7.5Hz,2H),3.11(t,J=7.5Hz,2H),2.32-2.20(m,2H),2.28(s,3H),2.20(s, 3H),1.82-1.60(m,4H),1.60-1.36(m,4H),0.99(t,J=7.2Hz,3H),0.98(t,J=7.2Hz, 3H).
实施例2(48)
8-(2-丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.40(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.36(brd,J=9.9Hz,1H),7.12 and 7.11(d, J=8.4Hz,两个构象异构体,1H),6.88(d,J=2.7Hz,1H),6.81(dd,J=8.4,2.7Hz, 1H),4.18(m,1H),3.83(s,3H),3.48(t,J=7.5Hz,2H),3.16(t,J=7.5Hz,2H),2.40- 2.20(m,2H),2.28(s,3H),2.19 and 2.18(s,两个构象异构体,3H),1.80(m,2H), 1.48 and 1.47(d,J=6.6Hz,两个构象异构体,3H),1.09 and 1.08(t,J=7.2Hz,两 个构象异构体,3H).
实施例2(49)
8-(N-丙基-N-环丙基甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.42(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.13(m,1H),6.88(brs,1H),6.82(m,1H), 3.88(m,2H),3.83(brs,3H),3.77(brs,2H),3.37(m,2H),3.06(m,2H),2.29(s,3H), 2.24(m,2H),2.19(s,3H),1.73(m,2H),1.12(m,1H),0.96(m,3H),0.62(m,2H), 0.26(brs,2H).
实施例2(50)
8-(3-戊氨基)-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶盐酸
TLC:Rf0.46(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,DMSO-d6):δ9.25(m,1H),8.31(s,1H),7.23(d,J=8.1Hz, 1H),6.95(d,J=2.4Hz,1H),6.86(dd,J=2.4,8.1Hz,1H),3.99(m,1H),3.78(s,3H), 3.15(m,2H),3.02(t,J=7.8Hz,2H),2.20(s,3H),2.18(m,2H),1.60-1.88(m,4H), 0.89(t,J=7.5Hz,6H).
实施例2(51)
8-[(2R)-1-甲氧基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.21(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.63(brd,J=8.4Hz,1H),7.09(d,J=8.7Hz,1H), 6.87(d,J=2.7Hz,1H),6.79(dd,J=8.7,2.7Hz,1H),4.19(m,1H),3.81(s,3H),3.65- 3.53(m,2H),3.45(t,J=8.1Hz,2H),3.43 and 3.41(s,两个构象异构体,3H),3.26- 3.01(m,2H),2.30-2.20(m,2H),2.28(s,3H),2.18(s,3H),1.96-1.58(m,2H),1.08 and 1.07(t,J=7.5Hz,两个构象异构体,3H).
实施例2(52)
8-[(2S)-1-甲氧基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.21(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.59(brd,J=10.2Hz,1H),7.11(d,J=8.4Hz,1H), 6.88(d,J=2.4Hz,1H),6.81(dd,J=8.4,2.7Hz,1H),4.19(m,1H),3.83(s,3H),3.66- 3.53(m,2H),3.48(t,J=8.1Hz,2H),3.44 and 3.42(s,两个构象异构体,3H),3.26- 3.02(m,2H),2.30-2.20(m,2H),2.29(s,3H),2.20(s,3H),1.98-1.69(m,2H),1.09 and 1.08(t,J=7.5Hz,两个构象异构体,3H).
实施例2(53)
8-环戊氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.30(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.7Hz,1H),6.84(d,J=2.7Hz,1H), 6.77(dd,J=8.7,2.7Hz,1H),6.34(brd,J=9.0Hz,1H),4.38(m,1H),3.82(s,3H), 3.15(t,J=7.2Hz,2H),2.89(t,J=7.8Hz,2H),2.30(s,3H),2.17(s,3H),2.18-2.00(m, 4H),1.95-1.65(m,6H).
实施例2(54)
8-(3-戊氨基)-2-甲基-3-(2,4-二氟苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶
TLC:Rf0.57(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.50(ddd,J=6.6,8.4,8.4Hz,1H),6.86-6.99(m, 2H),6.23(d,J=10.8Hz,1H),3.80(m,1H),3.09(t,J=7.2Hz,2H),2.92(t,J=8.1Hz, 2H),2.39(d,J=1.5Hz,3H),2.15(m,2H),1.53-1.81(m,4H),1.01(t,J=7.2Hz,6H).
实施例2(55)
8-(3-戊氨基)-2-三氟甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf 0.42(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.33(br d,J=10.2Hz,1H),7.13(d,J=8.7Hz,1H), 6.89(d,J=2.4Hz,1H),6.81(dd,J=2.4,8.7Hz,1H),4.04(m,1H),3.83(s,3H), 3.56(m,2H),3.20(m,2H),2.33(m,2H),2.19(s,3H),1.70-2.22(m,4H),1.08(m, 6H).
实施例2(56)
8-(N-乙基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.20(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=8.4,2.7Hz,1H),4.34-4.17(m,2H),3.91(q,J=7.2Hz,2H),3.83(s,3H), 3.68(t,J=5.1Hz,2H),3.47(t,J=7.8Hz,2H),3.32(s,3H),3.06(t,J=7.2Hz,2H), 2.28(s,3H),2.30-2.20(m,2H),2.18(s,3H),1.38(t,J=7.2Hz,3H).
实施例2(57)
8-环己氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.30(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.84(d,J=2.7Hz,1H), 6.77(dd,J=8.1,2.7Hz,1H),6.34(brd,J=9.6Hz,1H),3.81(s,3H),3.80(m,1H), 3.10(t,J=7.2Hz,2H),2.88(t,J=7.8Hz,2H),2.30(s,3H),2.17(s,3H),2.18-2.00(m, 4H),1.90-1.80(m,2H),1.75-1.60(m,1H),1.50-1.20(m,5H).
实施例2(58)
8-(N-丙基-N-(3-戊基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.43(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=8.1,2.7Hz,1H),4.20(m,1H),3.83(s,3H),3.60(m,2H),3.38(t, J=7.5Hz,2H),2.97(t,J=7.5Hz,2H),2.30-2.15(m,2H),2.27(s,3H),2.20(s,3H), 2.00-1.70(m,4H),1.42(m,2H),0.98(t,J=7.5Hz,6H),0.90(t,J=7.5Hz,3H).
实施例2(59)
8-(3-戊氨基)-2-甲基-3-(4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶
TLC:Rf0.57(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.60(d,J=9.0Hz,2H),6.99(d,J=9.0Hz,2H), 6.10(br d,J=10.5Hz,1H),3.84(s,3H),3.81(m,1H),3.08(t,J=7.2Hz,2H),2.94(t, J=7.8Hz,2H),2.53(s,3H),2.15(m,2H),1.53-1.82(m,4H),1.00(t,J=7.2Hz, 6H),.。
实施例2(60)
8-(3-戊氨基)-2-异丙基-3-(4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.54(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.48(d,J=8.7Hz,2H),6.97(d,J=8.7Hz,2H), 6.29(br d,J=10.5Hz,1H),3.84(s,3H),3.80(m,1H),3.32(sept,J=6.9Hz,1H), 3.07(t,J=7.2Hz,2H),2.91(t,J=7.5Hz,2H),2.13(m,2H),1.63-1.83(m,4H), 1.33(d,J=6.9Hz,6H),1.01(t,J=7.5HZ,6H).
实施例2(61)
8-t-丁氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.35(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.15(brd,J=8.7Hz,1H),6.97(brs,1H),6.85(d, J=2.7Hz,1H),6.78(dd,J=8.7,2.7Hz,1H),3.81(s,3H),3.15(t,J=7.2Hz,2H), 2.91(t,J=7.5Hz,2H),2.30(s,3H),2.18(s,3H),2.11(m,2H),1.57(s,9H).
实施例2(62)
8-(3-戊氨基)-3-(2,4,6-三甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶盐酸
TLC:Rf0.58(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.91(s,1H),7.39(brd,J=10.2Hz,1H),6.99(s, 2H),4.03(m,1H),3.52(t,J=7.8Hz,2H),3.17(t,J=7.2Hz,2H),2.32(s,3H), 2.31(m,2H),2.13(s,6H),1.67-1.96(m,4H),1.07(t,J=7.5Hz,6H).
实施例2(63)
8-(1-环丁基乙基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.28(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,吡啶-d5 0.5ml+CDCl3 0.1ml):δ7.46(d,J=8.1Hz,1H), 7.06(d,J=2.7Hz,1H),6.97(dd,J=8.1,2.7Hz,1H),6.80(d,J=10.2Hz,1H),3.96(m, 1H),3.74(s,3H),2.97(ddd,J=14.1,7.2,7.2Hz,2H),2.86(t,J=7.5Hz,2H),2.50- 2.36(m,1H),2.47(s,3H),2.39(s,3H),2.05-1.65(m,8H),1.15(d,J=6.3Hz,3H).
实施例2(64)
8-(3-戊氨基)-2-甲基-3-(2,3-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.37(苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.08(d,J=8.1Hz,1H),6.78(d,J=8.1Hz,1H), 6.21(d,J=10.8Hz,1H),3.84(s,3H),3.81(m,1H),3.08(t,J=6.6Hz,2H),2.88(t, J=8.1Hz,2H),2.29(s,3H),2.21(s,3H),2.13(m,2H),2.10(s,3H),1.56-1.82(m, 4H),1.03(t,J=7.5Hz,3H),1.01(t,J=6.9Hz,3H).
实施例2(65)
8-(3-戊氨基)-2-甲基-3-(2,5-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.43(苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ6.99(s,1H),6.76(s,1H),6.20(d,J=10.5Hz,1H), 3.84(s,3H),3.82(m,1H),3.08(t,J=6.9Hz,2H),2.89(t,J=7.2Hz,2H),2.31(s,3H), 2.19(s,3H),2.17(s,3H),2.14(m,2H),1.54-1.80(m,4H),1.01(m,6H).
实施例2(66)
8-(N-(2,2,2-三氟乙基)-N-环丙基甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.62(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.17(d,J=8.1Hz,1H),6.87(d,J=2.7Hz,1H), 6.80(dd,J=8.1,2.7Hz,1H),4.64(q,J=9.6Hz,2H),3.82(s,3H),3.41(d,J=6.6Hz, 2H),2.98(t,J=6.9Hz,2H),2.94(t,J=7.5Hz,2H),2.34(s,3H),2.21-2.09(m,2H), 2.18(s,3H),1.03(m,1H),0.57(m,2H),0.21(m,2H).
实施例2(67)
8-(2,2,2-三氟乙基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.22(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=8.1,2.7Hz,1H),6.75(brt,J=7.8Hz,1H),4.22(dq,J=7.8,7.8Hz,2H), 3.82(s,3H),3.12(t,J=7.5Hz,2H),2.92(t,J=7.8Hz,2H),2.31(s,3H),2.23-2.09(m, 2H),2.17(s,3H).
实施例2(68)
8-[(2R)-1-甲氧基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.25(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,吡啶-d5 0.5ml+CDCl3 0.1ml):δ7.39(d,J=8.1Hz,1H), 7.37(brd,J=9.3Hz,1H),7.03(d,J=2.7Hz,1H),6.95(dd,J=8.1,2.7Hz,1H),5.45(d, J=9.9Hz,1H),5.35(d,J=9.9Hz,1H),4.98(brs,2H),3.74(s,3H),3.63-3.48(m, 3H),3.26(s,3H),2.41(s,3H),2.34(s,3H),1.82-1.60(m,2H),0.97(t,J=7.5Hz, 3H).
实施例2(69)
8-[(2R)-1-甲氧基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-2,3-二 氢-呋[3,2-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,吡啶-d5 0.5ml+CDCl3 0.1ml):δ7.40(d,J=8.4Hz,1H), 7.03(brs,1H),6.95(dd,J=8.4,2.4Hz,1H),6.80(brd,J=9.3Hz,1H),4.47(m,1H), 4.47(t,J=8.4Hz,2H),3.74(s,3H),3.56(d,J=4.8Hz,2H),3.28(s,3H),3.12(t, J=8.4Hz,2H),2.43(s,3H),2.35(s,3H),1.87-1.46(m,2H),1.00(t,J=7.5Hz,3H).
实施例2(70)
8-(3-戊氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.33(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.90(s,1H),7.39(br d,J=10.2Hz,1H),6.72(s, 2H),4.02(m,1H),3.81(s,3H),3.53(t,J=7.8Hz,2H),3.17(t,J=6.9Hz,2H), 2.32(m,2H),2.14(s,6H),1.66-1.96(m,4H),1.08(t,J=7.2Hz,6H).
实施例2(71)
8-(3-戊氨基)-3-(4,6-二甲基-2-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.33(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.99(s,1H),7.37(br d,J=10.8Hz,1H),6.75(s, 1H),6.70(s,1H),4.01(m,1H),3.85(s,3H),3.57(t,J=7.8Hz,2H),3.16(t,J=7.2Hz, 2H),2.36(s,3H),2.31(m,2H),2.23(s,3H),1.63-1.92(m,4H),1.06(t,J=7.2Hz, 6H).
实施例2(72)
8-(3-戊氨基)-2-甲基-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.33(苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ6.68(s,2H),6.21(d,J=10.5Hz,1H),3.81(m,1H), 3.80(s,3H),3.09(t,J=7.2Hz,2H),2.88(t,J=7.8Hz,2H),2.19(s,3H),2.13(m,2H), 2.04(s,6H),1.55-1.83(m,4H),1.03(t,J=7.5Hz,6H).
实施例2(73)
8-(3-戊氨基)-2-甲基-3-(4,6-二甲基-2-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.33(苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ6.75(m,1H),6.62(s,1H),6.21(d,J=10.5Hz,1H), 3.80(m,1H),3.71(s,3H),3.06(m,2H),2.87(m,2H),2.34(s,3H),2.24(s,3H), 2.12(m,2H),2.09(s,3H),1.53-1.80(m,4H),1.03(t,J=7.2Hz,3H),1.00(t, J=7.5Hz,3H).
实施例2(74)
8-(3-甲基戊-3-基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.36(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.01(brs,1H),7.12(d,J=8.1Hz,1H),6.89(d, J=2.7Hz,1H),6.82(dd,J=8.1,2.7Hz,1H),3.83(s,3H),3.52(t,J=7.8Hz,2H), 3.16(t,J=7.2Hz,2H),2.28(s,3H),2.24(m,2H),2.20(s,3H),2.00-1.85(m,4H), 1.55(s,3H),1.03(t,J=7.5Hz,6H).
实施例2(75)
8-(3-戊氨基)-2-甲基-3-(5-氯-1,3-二氧杂茚满-6-基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.44(苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ6.96(s,1H),6.85(s,1H),6.22(br d,J=10.5Hz, 1H),5.99(s,2H),3.80(m,1H),3.08(t,J=7.2Hz,2H),2.91(t,J=7.8Hz,2H),2.34(s, 3H),2.16(m,2H),1.53-1.81(m,4H),1.01(t,J=7.2Hz,6H).
实施例2(76)
8-(N-乙基-N-苄氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.43(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.26-7.43(m,5H),7.13(d,J=8.4Hz,1H),6.89(d, J=2.7Hz,1H),6.83(dd,J=2.7,8.4Hz,1H),5.21(s,2H),3.87(q,J=6.9Hz,2H), 3.83(s,3H),3.47(t,J=7.2Hz,2H),3.03(t,J=7.2Hz,2H),2.29(s,3H),2.22(m,2H), 2.19(s,3H),1.39(t,J=6.9Hz,3H).
实施例2(77)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-三氟甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.52(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,pyridene-d5(0.5ml),CDCl3(0.1ml)):δ7.71(d,J=8.4Hz,1H), 7.57(m,1H),7.28(m,1H),6.77(d,J=10.5Hz,1H),3.74(m,1H),2.95(t,J=7.5Hz, 2H),2.85(t,J=7.8Hz,2H),2.46(s,3H),1.98(m,2H),1.64-1.48(m,4H),0.92(t, J=7.5Hz,6H).
实施例2(78)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.20(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,pyridene-d5(0.5ml),CDCl3(0.1ml)):δ7.59(d,J=8.4Hz,1H), 7.24(d,J=2.4Hz,1H),6.98(dd,J=8.4,2.4Hz,1H),6.78(d,J=10.5Hz,1H),3.74(m, 1H),3.69(s,3H),2.94(t,J=7.2Hz,2H),2.85(t,J=7.8Hz,2H),2.51(s,3H),1.96(m, 2H),1.64-1.48(m,4H),0.91(t,J=7.5Hz,6H).
实施例2(79)
8-(N-苄基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.24(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34-7.44(m,3H),7.27-7.34(m,2H),7.13(d, J=8.4Hz,1H),6.90(d,J=2.7Hz,1H),6.83(dd,J=2.7,8.4Hz,1H),5.11(s,2H), 4.14(t,J=4.8Hz,2H),3.84(s,3H),3.64(t,J=4.8Hz,2H),3.49(t,J=7.8Hz,2H), 3.29(s,3H),3.07(t,J=7.2Hz,2H),2.31(s,3H),2.23(m,2H),2.19(s,3H).
实施例2(80)
8-(1,2,5,6-四氢吡啶基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.30(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=2.7,8.1Hz,CDCl3),5.97(m,1H),5.83(m,1H),4.21(m,2H),3.85(m, 2H),3.82(s,3H),3.07(t,J=7.2Hz,2H),2.89(t,J=7.5H z,2H),2.41(m,2H),2.32(s, 3H),2.16(s,3H),2.11(m,2H).
实施例2(81)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基-4,5-二甲苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.29(brd,J=10.2Hz,1H),7.04(s,1H),6.83(s,1 H),3.95(m,1H),3.90(s,3H),3.56(t,J=7.8Hz,2H),3.12(t,J=7.5Hz,2H), 2.42(s,3H),2.31(s,3H),2.28(m,2H),2.24(s,3H),1.90-1.62(m,4H),1.04(t, J=7.5Hz,6H).
实施例2(82)
8-(1,2,3,4-四氢异喹啉-2-基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.24(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.23-7.18(m,3H),7.16(d,J=8.4Hz,1H), 7.11(m,1H),6.86(d,J=2.4Hz,1H),6.79(dd,J=8.4,2.4Hz,1H),4.86(s,2H), 4.09(t,J=5.7Hz,2H),3.82(s,3H),3.08(t,J=5.7Hz,2H),2.97(t,J=7.2Hz,2H), 2.89(t,J=7.8Hz,2H),2.33(s,3H),2.17(s,3H),2.08(m,2H).
实施例2(83)
8-苯氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.35(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.01(br,1H),7.45-7.38(m,2H),7.33-7.17(m, 4H),6.87(d,J=2.4Hz,1H),6.80(dd,J=8.1,2.4Hz,1H),3.83(s,3H),2.89(t, J=7.8Hz,2H),2.35(s,3H),2.30(t,J=7.5Hz,2H),2.21(s,3H),2.02-1.90(m,2H).
实施例2(84)
8-(2-甲基苯基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.37(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.76(br,1H),7.32-7.17(m,5H),6.87(d,J=2.4Hz, 1H),6.80(dd,J=8.4,2.4Hz,1H),3.83(s,3H),2.85(t,J=7.5Hz,2H),2.36(s,6H), 2.22(s,3H),2.13(t,J=7.5Hz,2H),1.96-1.85(m,2H).
实施例2(85)
8-(3-甲基苯基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.38(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.96(br,1H),7.32-7.26(m,1H),7.19(d,J=8.4Hz, 1H),7.12-7.01(m,3H),6.87(d,J=2.7Hz,1H),6.80(dd,J=8.4,2.7Hz,1H),3.83(s, 3H),2.88(t,J=7.8Hz,2H),2.40(s,3H),2.35(s,3H),2.31(t,J=6.9Hz,2H),2.21(s, 3H),2.02-1.91(m,2H).
实施例2(86)
8-(4-甲基苯基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.33(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.93(br,1H),7.23-7.11(m,5H),6.87(d,J=2.7Hz, 1H),6.80(dd,J=8.4,2.7Hz,1H),3.83(s,3H),2.86(t,J=7.5Hz,2H),2.40(s,3H), 2.35(s,3H),2.29(t,J=7.5Hz,2H),2.21(s,3H),2.00-1.88(m,2H).
实施例2(87)
8-(N-苯基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.31-7.24(m,2H),7.21(d,J=8.4Hz,1H),6.99- 6.87(m,4H),6.81(dd,J=8.4,2.7Hz,1H),4.15-4.07(m,2H),3.84(s,3H),2.92(t, J=7.5Hz,2H),2.36(s,3H),2.31(t,J=7.5Hz,2H),2.22(s,3H),2.05-1.94(m,2H), 1.82-1.68(m,2H),0.96(t,J=7.2Hz,3H).
实施例2(88)
8-(N-苄基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.63(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.33-7.21(m,5H),7.19(d,J=8.4Hz,1H),6.87(d, J=2.7Hz,1H),6.80(dd,J=8.4,2.7Hz,1H),4.86(s,2H),3.83(s,3H),3.42-3.34(m, 2H),2.88(t,J=7.8Hz,2H),2.81(t,J=7.1Hz,2H),2.36(s,3H),2.20(s,3H),2.11- 1.98(m,2H),1.67-1.54(m,2H),0.88(t,J=7.5Hz,3H).
实施例2(89)
8-(N,N-二烯丙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=2.7,8.4Hz,1H),6.03(m,2H),5.40(d,J=10.5Hz,2H),5.35(d,J=18Hz, 2H),4.49(d,J=6.0Hz,4H),3.83(s,3H),3,47(t,J=7.8Hz,2H),3.08(t,J=7.2Hz, 2H),2.28(s,3H),2.23(m,2H),2.18(s,3H).
实施例2(90)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-二甲氨基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.17(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.1Hz,1H),6.70(d,J=2.7Hz,1H), 6.64(dd,J=8.1,2.7Hz,1H),6.19(d,J=10.2Hz,1H),3.80(m,1H),3.08(t, J=7.5Hz,2H),2.95(s,6H),2.89(t,J=7.5Hz,2H),2.32(s,3H),2.18(s,3H), 2.18-2.08(m,2H),1.80-1.56(m,4H),1.01(brs,6H).
实施例2(91)
8-(1-苯基丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.83(d,J=8.7Hz,1H),7.27-7.48(m,5H),7.12(d, J=8.4Hz,1H),6.88(m,1H),6.81(dd,J=2.7,8.4Hz,1H),5.10(m,1H),3.82(s,3H), 3.41(m,2H),3.16(m,1H),2.83(m,1H),2.32(s,3H),2.20 and 2.19(s,total 3H), 2.12(m,4H),1.12 and 1.01(t,J=7.2Hz,total 3H).
实施例2(92)
8-(N-(2-苯基乙基)-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.35(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.23-7.05(m,6H),6.90(d,J=2.4Hz,1H), 6.83(dd,J=8.4,2.4Hz,1H),4.33(t,J=6.6Hz,2H),3.84(s,3H),3.71(t,J=6.9Hz, 2H),3.37(t,J=7.5Hz,2H),2.98(t,J=7.2Hz,2H),2.77(t,J=7.5Hz,2H),2.32(s, 3H),2.20(s,3H),2.20-2.06(m,2H),1.81-1.68(m,2H),0.97(t,J=7.5Hz,3H).
实施例2(93)
8-(N-(3-苯基丙基)-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.40(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.26-7.05(m,6H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),3.83(s,3H),3.66-3.53(m,4H),2.88(t,J=7.5Hz,2H), 2.87(t,J=7.5Hz,2H),2.62(t,J=7.8Hz,2H),2.32(s,3H),2.19(s,3H),2.15-2.04(m, 2H),1.95-1.83(m,2H),1.61-1.49(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(94)
8-(N-(4-苯基丁基)-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.25-7.05(m,6H),6.86(d,J=2.7Hz,1H), 6.78(dd,J=8.1,2.7Hz,1H),3.83(s,3H),3.63(t,J=6.6Hz,2H),3.57-3.49(m,2H), 2.90(t,J=7.5Hz,2H),2.88(t,J=7.5Hz,2H),2.57(t,J=6.9Hz,2H),2.32(s,3H), 2.19(s,3H),2.15-2.05(m,2H),1.66-1.49(m,6H),0.88(t,J=7.5Hz,3H).
实施例2(95)
8-(1-苯基-2-丁基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.41(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,DMSO-d6):δ9.24(m,1H),7.04-7.30(m,6H),6.95(brs, 1H),6.86(dd,J=2.7,8.4Hz,1H),4.20(brs,1H),3.78(s,3H),2.87-3.17(m,3H), 2.64-2.87(m,3H),2.26(s,3H),1.82-2.18(m,5H),1.63-1.82(m,2H),0.93(br t, J=6.9Hz,3H).
实施例2(96)
8-(1-苯基-3-戊基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.43(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,DMSO-d6):δ8.53(m,1H),7.09-7.28(m,6H),6.96(d, J=3.0Hz,1H),6.85(dd,J=3.0,8.4Hz,1H),4.10(m,1H),3.82(s,3H),2.89-3.02(m, 3H),2.68-2.85(m,3H),2.25(s,3H),2.00-2.22(m,7H),1.79(m,2H),0.93(t, J=7.5Hz,3H).
实施例2(97)
8-(N-(4-甲基苯基)-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.43(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.27(d,J=8.1Hz,2H),7.13-7.22(m,3H),6.90(d, J=2.4Hz,1H),6.84(dd,J=2.4,8.7Hz,1H),4.46(m,2H),3.84(s,3H),3.35(m,2H), 2.43(s,3H),2.31(s,3H),2.22(s,3H),1.77-1.97(m,6H),0.98(t,J=7.5Hz,3H).
实施例2(98)
8-(N-(4-甲基苯基)甲基-N-丙氨基)-2-甲基-3-(2-甲基4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.11-7.21(m,5H),6.90(d,J=2.7Hz,1H), 6.83(dd,J=2.7,8.7Hz,1H),5.13(s,2H),3.84(s,3H),3.72(t,J=7.5Hz,2H),3.48(t, J=8.1Hz,2H),3.01(t,J=6.9Hz,2H),2.36(s,3H),2.29(s,3H),2.22(m,2H),2.19(s, 3H),1.77(m,2H),0.94(t,J=7.5Hz,3H).
实施例2(99)
8-(N-(3-甲基苯基)-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.41(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.36(m,1H),7.06-7.24(m,4H),6.91(d,J=2.4Hz, 1H),6.84(dd,J=2.4,8.1Hz,1H),4.46(m,2H),3.84(s,3H),3.36(m,2H),2.42(s, 3H),2.32(s,3H),2.23(s,3H),1.77-2.00(m,6H),0.99(t,J=7.2Hz,3H).
实施例2(100)
8-(N-(4-甲氧基苯基)甲基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.18(d,J=8.7Hz,2H),7.13(d,J=8.4Hz,1H), 6.90(d,J=8.7Hz,2H),6.90(d,J=3.0Hz,1H),6.83(dd,J=3.0,8.4Hz,1H),5.10(s, 2H),3.84(s,3H),3.82(s,3H),3.70(t,J=7.5Hz,2H),3.49(t,J=8.1Hz,2H),3.01(t, J=6.9Hz,2H),2.30(s,3H),2.22(m,2H),2.19(s,3H),1.75(m,2H),0.93(t, J=7.2Hz,3H).
实施例2(101)
8-(N-(4-氯苯基)甲基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.37(d,J=8.7Hz,2H),7.24(d,J=8.7Hz,2H), 7.12(d,J=8.4Hz,1H),6.90(d,J=2.7Hz,1H),6.83(dd,J=2.7,8.4Hz,1H),5.15(s, 2H),3.83(s,3H),3.68(m,2H),3.50(t,J=7.8Hz,2H),3.02(t,J=7.2Hz,2H),2.29(s, 3H),2.25(m,2H),2.19(s,3H),1.74(m,2H),0.93(t,J=7.2Hz,3H).
实施例2(102)
8-(N-(2-甲基苯基)-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.46(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.27-7.45(m,4H),7.16(d,J=8.4Hz,1H),6.90(d, J=2.4Hz,1H),6.84(dd,J=2.4,8.4Hz,1H),4.53(m,1H),4.37(m,1H),3.84(s,3H), 3.34(m,2H),2.31(s,3H),2.23(s,3H),2.10(s,3H),1.50-2.07(m,6H),0.97(t, J=7.5Hz,3H).
实施例2(103)
8-((3S)-3-甲氧基甲基-1,2,3,4-四氢异喹啉-2-基)-2-甲基-3-(2-甲基-4-甲 氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.56(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.30-7.05(m,5H),6.90-6.75(m,2H),5.48(m, 1H),5.03(d,J=15.6Hz,1H),4.72(dd,J=15.6,3.9Hz,1H),3.82(s,3H),3.33 and 3.32(s,3H),3.87-3.05(m,7H),2.82(d,J=15.6Hz,1H),2.40-2.10(m,2H),2.29(s, 3H),2.25 and 2.11(s,3H).
实施例2(104)
8-(3-戊氨基)-2-甲基-3-(2-二甲氨基-4-甲基吡啶-5-基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.42(氯仿∶甲醇=20∶1);
NMR(300MHz,CDCl3):δ8.01(s,1H),7.32(d,J=10.2Hz,1H),6.85(s,1H), 4.00(m,1H),3.41(s,6H),3.40(m,2H),3.17(m,2H),2.37(s,3H),2.33(m,2H), 2.32(s,3H),1.65-1.95(m,4H),1.07(t,J=7.5Hz,3H),1.06(t,J=7.2Hz,3H).
实施例2(105)
8-((2S)-1-甲氧基-3-苯基-2-丙基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.77(m,1H),7.25-7.36(m,3H),7.16-7.23(m, 2H),7.11(m,1H),6.88(m,1H),6.80(m,1H),4.44(m,1H),3.82(s,3H),3.53- 3.68(m,2H),3.47and 3.46(s,3H),3.38(m,2H),3.11(t,J=7.2Hz,2H),3.08(m, 1H),2.81(m,1H),2.31(s,3H),2.20 and 2.17(s,3H),2.15(m,2H).
实施例2(106)
8-(N-(4-甲基硫苯基)甲基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.50(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.25(d,J=8.4Hz,2H),7.18(d,J=8.4Hz,2H), 7.13(d,J=8.1Hz,1H),6.90(d,J=2.4Hz,1H),6.83(dd,J=2.4,8.1Hz,1H),5.13(s, 2H),3.84(s,3H),3.70(m,2H),3.50(t,J=7.8Hz,2H),3.01(t,J=6.9Hz,2H),2.50(s, 3H),2.29(s,3H),2.23(m,2H),2.19(s,3H),1.75(m,2H),0.93(t,J=7.5Hz,3H).
实施例2(107)
8-(4-苯基哌嗪-1-基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.30(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,DMSO-d6):δ7.30-7.38(m,2H),7.21-7.29(m,2H),7.12(d, J=8.4Hz,1H),7.00(brd,J=6.9Hz,1H),6.95(d,J=2.7Hz,1H),6.86(dd,J=2.7, 8.4Hz,1H),4.22(brs,4H),3.79(s,3H),3.53(brs,4H),3.14(m,2H),2.97(t, J=7.8Hz,2H),2.21(s,3H),2.15(m,2H),2.06(s,3H).
实施例2(108)
8-(4-(2-氯苯基)哌嗪-1-基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.38(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.41(dd,J=1.5,7.8Hz,1H),7.28(m,1H),7.16(d, J=8.1Hz,1H),7.15(d,J=8.7Hz,1H),7.03(m,1H),6.86(d,J=2.7Hz,1H),6.79(dd, J=2.7,8.1Hz,1H),3.90(m,4H),3.82(s,3H),3.33(t,J=4.8H,4H),3.16(t,J=7.5Hz, 2H),2.91(t,J=7.8Hz,2H),2.33(s,3H),2.17(s,3H),2.14(m,2H).
实施例2(109)
8-(N,N-二丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.57(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.12(d,J=7.8Hz,1H),6.89(d,J=2.4Hz,1H), 6.82(dd,J=2.4,7.8Hz,1H),3.90(t,J=7.5Hz,4H),3.83(s,3H),3.48(m,2H), 3.02(m,2H),2.27(s,3H),2.25(m,2H),2.19(s,3H),1.71(m,4H),1.38(m,4H), 0.97(t,J=6.9Hz,6H).
实施例2(110)
8-(N-甲基-N-丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.36(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.1Hz,1H),6.88(d,J=3.0Hz,1H), 6.81(dd,J=3.0,8.1Hz,1H),3.97(m,2H),3.83(s,3H),3.51(s,3H),3.45(t, J=8.1Hz,2H),3.12(t,J=6.9Hz,2H),2.26(s,3H),2.23(m,2H),2.18(s,3H), 1.85(m,2H),1.40(m,2H),0.99(t,J=7.2Hz,3H).
实施例2(111)
8-(N-(4-甲基苯基)甲基-N-丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10-7.21(m,5H),6.89(d,J=2.4Hz,1H), 6.83(dd,J=2.4,8.1Hz,1H),5.13(s,2H),3.83(s,3H),3.77(t,J=7.2Hz,2H),3.48(t, J=7.8Hz,2H),3.01(t,J=6.9Hz,2H),2.36(s,3H),2.29(s,3H),2.21(m,2H),2.19(s, 3H),1.73(m,2H),1.34(m,2H),0.93(t,J=7.2Hz,3H).
实施例2(112)
8-(N-(4-甲基苯基)甲基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧 基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.23(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.25-7.05(m,5H),6.98-6.78(m,2H),5.06(s, 2H),4.22-4.03(m,2H),3.84(s,3H),3.75-3.58(m,2H),3.58-3.38(m,2H),3.30(s, 3H),3.20-2.90(m,2H),2.36(s,3H),2.30(s,3H),2.21(m,2H),2.19(s,3H).
实施例2(113)
8-(N-环丙基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.35(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.25-6.95(m,5H),6.95-6.73(m,2H),5.40- 5.15(m,2H),3.83(s,3H),3.65-3.30(m,2H),3.30-2.95(m,2H),2.35(s,3H), 2.31(s,3H),2.30-2.10(m,3H),2.19(s,3H),1.10-0.80(m,4H).
实施例2(114)
8-(N-环丙基甲基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.37(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30-7.00(m,5H),7.00-6.75(m,2H),5.24(s, 2H),3.84(s,3H),3.80-3.60(m,2H),3.60-3.35(m,2H),3.20-2.90(m,2H),2.34(s, 3H),2.29(s,3H),2.22(s,2H),2.11(s,3H),1.38-1.05(m,1H),0.75-0.50(m,2H), 0.35-0.10(m,2H).
实施例2(115)
8-(N,N-二丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.59(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.17(d,J=8.4Hz,1H),6.86(d,J=2.4Hz,1H), 6.79(dd,J=2.4,8.4Hz,1H),3.82(s,3H),3.56(m,4H),2.95(t,J=7.2Hz,2H), 2.90(t,J=7.8Hz,2H),2.33(s,3H),2.19(s,3H),2.13(m,2H),1.58(m,4H),0.89(t, J=7.5Hz,6H).
实施例2(116)
8-(N-(4-甲基苯基)甲基-N-(2-丁炔基)氨基)-2-甲基-3-(2-甲基4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33(d,J=8.1Hz,2H),7.19(d,J=8.1Hz,2H), 7.11(d,J=8.7Hz,1H),6.89(d,J=2.7Hz,1H),6.82(dd,J=2.7,8.7Hz,1H),5.27(d, J=15.0Hz,1H),5.24(d,J=15.0Hz,1H),4.41(m,2H),3.83(s,3H),3.51(t, J=7.5Hz,2H),3.22(t,J=6.9Hz,2H),2.37(s,3H),2.28(s,3H),2.25(m,2H),2.17(s, 3H),1.91(t,J=2.4Hz,3H).
实施例2(117)
8-(N-丙基-N-(2-丁炔基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.55(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=2.7,8.1Hz,1H),4.40(m,2H),3.82(s,3H),3.55(m,2H),3.11(t, J=7.2Hz,2H),2.91(t,J=7.8Hz,2H),2.32(s,3H),2.18(s,3H),2.13(m,2H),1.81(t, J=2.4Hz,3H),1.66(m,2H),0.95(t,J=7.5Hz,3H).
实施例2(118)
8-(5-壬基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.58(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33(brd,J=10.5Hz,1H),7.12(d,J=8.7Hz,1H), 6.88(d,J=2.7Hz,1H),6.81(dd,J=2.7,8.7Hz,1H),4.10(m,1H),3.83(s,3H), 3.49(t,J=8.1Hz,2H),3.12(t,J=6.6Hz,2H),2.29(s,3H),2.27(m,2H),2.20(s,3H), 1.61-1.88(m,4H),1.30-1.53(m,8H),0.94(m,6H).
实施例2(119)
8-(N-环戊基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.38(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CD3OD):δ7.20-6.98(m,5H),6.93(d,J=2.4Hz,1H), 6.85(dd,J=8.6,2.4Hz,1H),5.20(d,J=16.5Hz,1H),5.09(d,J=16.5Hz,1H),5.02- 4.70(m,1H),3.81(s,3H),3.17(t,J=7.2Hz,2H),2.98(t,J=7.8Hz,2H),2.29(s,3H), 2.22(s,3H),1.98(s,3H),2.40-1.60(m,10H).
实施例2(120)
8-(N-环丙基甲基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基 苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.85(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.28-7.16(m,5H),6.87(d,J=3.0Hz,1H), 6.79(dd,J=3.0,8.4Hz,1H),4.89(s,2H),3.83(s,3H),3.38(d,J=6.9Hz,2H),2.96(t, J=7.2Hz,2H),2.89(t,J=7.2Hz,2H),2.47(s,3H),2.36(s,3H),2.19(s,3H), 2.09(quint,J=7.2Hz,2H),1.10-0.95(m,1H),0.52-0.42(m,2H),0.10-0.05(m, 2H).
实施例2(121)
8-(N-(4-氟苯基)甲基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.87(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.28-7.16(m,3H),7.03-6.95(m,2H),6.87(d, J=2.4Hz,1H),6.79(dd,J=2.4,8.4Hz,1H),4.80(s,2H),3.83(s,3H),3.40-3.32(m, 2H),2.89(t,J=7.5Hz,2H),2.81(t,J=7.5Hz,2H),2.36(s,3H),2.20(s,3H), 2.07(quint,J=7.5Hz,2H),1.62-1.50(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(122)
8-(N-环丁基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.19(d,J=8.4Hz,1H),7.02(d,J=7.5Hz,2H), 6.89(d,J=7.5Hz,2H),6.87(d,J=3.0Hz,1H),6.80(dd,J=8.4,3.0Hz,1H),4.90- 4.70(m,2H),4.08(m,1H),3.83(s,3H),2.84(t,J=7.5Hz,2H),2.61(m,2H),2.39(s, 3H),2.30(s,3H),2.19(s,3H),2.20-2.06(m,4H),1.96(m,2H),1.80-1.60(m,2H).
实施例2(123)
8-(N-乙基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.69(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.19(d,J=8.1Hz,1H),7.14-7.06(m,4H),6.87(d, J=2.7Hz,1H),6.80(dd,J=2.7,8.1Hz,1H),4.81(s,2H),3.87(s,3H),3.47(q, J=6.9Hz,2H),2.88(t,J=7.8Hz,2H),2.81(brt,J=7.8Hz,2H),2.36(s,3H),2.33(s, 3H),2.20(s,3H),2.04(quint,J=7.8Hz,2H),1.18(t,J=6.9Hz,3H).
实施例2(124)
8-(N-丙基-N-(4-三氟甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.79(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.57(brd,J=8.1Hz,2H),7.44(brd,J=8.1Hz,2H), 7.18(d,J=8.7Hz,1H),6.87(d,J=2.4Hz,1H),6.79(dd,J=2.4,8.7Hz,1H),4.91(s, 2H),3.83(s,3H),3.49-3.25(m,2H),2.90(t,J=7.8Hz,2H),2.87(t,J=7.8Hz,2H), 2.35(s,3H),2.19(s,3H),2.18-2.00(m,2H),1.62-1.50(m,2H),0.88(t,J=7.5Hz, 3H).
实施例2(125)
8-(N-丙基-N-(四氢呋喃-2-基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.31(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.78(dd,J=2.7,8.1Hz,1H),3.84-4.06(m,2H),3.82(s,3H),3.64-3.80(m,3H), 3.50-3.64(m,2H),2.99(t,J=7.2Hz,2H),2.91(t,J=8.1Hz,2H),2.32(s,3H),2.19(s, 3H),2.13(m,2H),1.74-2,00(m,3H),1.42-1.65(m,3H),0.89(t,J=7.5Hz,3H).
实施例2(126)
8-(N-丁基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.30(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=2.7,8.4Hz,1H),3.92(t,J=5.7Hz,2H),3.82(s,3H),3.57(m,2H), 3.50(t,J=5.7Hz,2H),3.28(s,3H),2.98(t,J=7.8Hz,2H),2.91(t,J=7.8Hz,2H), 2.32(s,3H),2.18(s,3H),2.13(m,2H),1.55(m,2H),1.33(m,2H),0.90(t,J=7.2Hz, 3H).
实施例2(127)
8-(N-丙基-N-环丙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=8.1,2.7Hz,1H),3.85(m,2H),3.82(s,3H),3.19(t,J=7.5Hz,2H), 3.07(m,1H),2.92(t,J=7.5Hz,2H),2.31(s,3H),2.18(s,3H),2.12(m,2H),1.62(m, 2H),0.89(t,J=7.2Hz,3H),0.80-0.68(m,4H).
实施例2(128)
8-(N-环丁基甲基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.57(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.17(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.78(dd,J=2.7,8.4Hz,1H),3.82(s,3H),3.82(t,J=6.0Hz,2H),3.64(d,J=7.5Hz, 2H),3.49(t,J=6.0Hz,2H),3.28(s,3H),2.96(t,J=7.2Hz,2H),2.91(t,J=7.8Hz, 2H),2.62-2.50(m,1H),2.32(s,3H),2.18(s,3H),2.20-2.05(m,2H),2.06-1.58(m, 6H).
实施例2(129)
8-(3-乙氧基羰基-1,2,5,6-四氢吡啶基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf 0.27(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.27(m,1H),7.09(d,J=8.1Hz,1H),6.88(d, J=2.7Hz,1H),6.81(dd,J=2.7,8.1Hz,1H),4.62(m,2H),4.27(q,J=6.9Hz,2H), 4.20(t,J=5.7Hz,2H),3.83(s,3H),3.47(t,J=7.2Hz,2H),3.16(t,J=6.0Hz,2H), 2.85(m,2H),2.27(s,3H),2.26(m,2H),2.17(s,3H),1.34(t,J=6.9HZ,3H).
实施例2(130)
8-(N-环丙基甲基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.68(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.21(d,J=7.8Hz,2H),7.16(d,J=7.8Hz,2H), 7.13(d,J=8.4Hz,1H),6.90(d,J=2.7Hz,1H),6.83(dd,J=2.7,8.4Hz,1H),5.41(brs, 2H),5.27(m,2H),5.22(brs,2H),3.83(s,3H),3.74(m,2H),2.37(s,3H),2.31(s, 3H),2.20(s,3H),1.24(m,1H),0.67(m,2H),0.24(m,2H).
实施例2(131)
8-(3-(3-甲基-1,2,4-噁二唑-5-基)-1,2,5,6-四氢吡啶基)-2-甲基-3-(2-甲 基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.18(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(m,1H),7.15(d,J=8.7Hz,1H),6.86(d, J=2.7Hz,1H),6.79(dd,J=2.7,8.7Hz,1H),4.57(m,2H),3.94(m,2H),3.82(s,3H), 3.09(t,J=7.5Hz,2H),2.91(t,J=7.8Hz,2H),2.71(m,2H),2.42(s,3H),2.32(s,3H), 2.17(s,3H),2.14(m,2H).
实施例2(132)
8-(4-庚氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.37(d,J=8.7Hz,1H),7.07(d,J=2.4Hz,1H), 6.97(dd,J=2.4,8.7Hz,1H),4.13(m,1H),3.85(s,3H),3.35-3.66(m,2H),3.13(t, J=7.5Hz,2H),2.34(s,3H),2.29(m,2H),1.60-1.84(m,4H),1.34-1.60(m,4H), 1.00(t,J=7.2Hz,3H),0.99(t,J=7.5Hz,3H).
实施例2(133)
8-(N-环丙基甲基-N-(2-丁酰基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.73(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.78(dd,J=8.1,2.7Hz,1H),4.54(brs,2H),3.82(s,3H),3.53(d,J=6.9Hz,2H), 3.13(t,J=7.2Hz,2H),2.91(t,J=7.8Hz,2H),2.33(s,3H),2.17(s,3H),2.17-2.08(m, 2H),1.81(t,J=2.7Hz,3H),1.20-1.16(m,1H),0.60-0.52(m,2H),0.36-0.28(m, 2H).
实施例2(134)
8-(N-(2-甲氧基乙基)-N-(2-丁酰基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.13(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),4.44-4.39(m,2H),3.92(t,J=6.0Hz,2H),3.82(s,3H), 3.65(t,J=6.0Hz,2H),3.34(s,3H),3.13(t,J=7.2Hz,2H),2.91(t,J=7.8Hz,2H), 2.32(s,3H),2.17(s,3H),2.17-2.08(m,2H),1.81(t,J=2.7Hz,3H).
实施例2(135)
8-(2-丁酰基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.80(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.85(d,J=2.4Hz,1H), 6.78(dd,J=8.4,2.4Hz,1H),6.53(t,J=6.9Hz,1H),4.36-4.30(m,2H),3.82(s,3H), 3.25(t,J=7.2Hz,2H),2.90(t,J=7.8Hz,2H),2.31(s,3H),2.18(s,3H),2.20- 2.08(m,2H),1.83(t,J=2.1Hz,3H).
实施例2(136)
8-(4-(4-氯苯基)-1,2,5,6-四氢吡啶基)-2-甲基-3-(2-甲基-4-甲氧基苯基)- 6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.10(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.42-7.30(m,4H),7.16(d,J=8.1Hz,1H),6.86(d, J=2.4Hz,1H),6.79(dd,J=8.1,2.4Hz,1H),6.22-6.18(m,1H),4.50-4.32(m,2H), 4.10-3.90(m,2H),3.82(s,3H),3.10(t,J=6.9Hz,2H),2.91(t,J=7.5Hz,2H),2.82- 2.69(m,2H),2.33(s,3H),2.17(s,3H),2.17-2.08(m,2H).
实施例2(137)
8-(N-环丙基甲基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.36(d,J=8.4Hz,1H),7.18(d,J=8.1Hz,2H), 7.15(d,J=8.1Hz,2H),7.08(d,J=2.7Hz,1H),6.97(dd,J=8.4,2.7Hz,1H),5.25(d, J=15.9Hz,1H),5.21(d,J=15.9Hz,1H),3.85(s,3H),3.70(m,2H),3.36-3.62(m, 2H),3.07(t,J=7.2Hz,2H),2.36(s,3H),2.35(s,3H),2.23(m,2H),1.23(m,1H), 0.63(m,2H),0.18(m,2H).
实施例2(138)
8-(N-丙基-N-(4-三氟甲基氧苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.55(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(brd,J=8.7Hz,2H),7.18(d,J=8.4Hz,1H), 7.15(brd,J=8.7Hz,2H),6.87(d,J=2.7Hz,1H),6.80(dd,J=8.4,2.7Hz,1H),4.84(s, 2H),3.83(s,3H),3.41-3.35(m,2H),2.89(t,J=7.5Hz,2H),2.83(t,J=7.8Hz,2H), 2.36(s,3H),2.19(s,3H),2.19-2.00(m,2H),1.66-1.54(m,2H),0.88(t,J=7.5Hz, 3H).
实施例2(139)
8-(N-(2-丁酰基)-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.40(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.05(d,J=2.4Hz,1H), 6.88(dd,J=8.7,2.4Hz,1H),4.54(q,J=2.1Hz,2H),3.83(s,3H),3.52(d,J=6.6Hz, 2H),3.13(t,J=7.5Hz,2H),2.92(t,J=7.5Hz,2H),2.37(s,3H),2.13(quint,J=7.5Hz, 2H),1.81(t,J=2.1Hz,3H),1.16-1.02(m,1H),0.60-0.52(m,2H),0.32-0.26(m, 2H).
实施例2(140)
8-(N-丙基-N-(3-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.27(m,1H),7.15(m,1H),7.13(d,J=8.1Hz,1H), 7.05(m,2H),6.90(d,J=2.7Hz,1H),6.83(dd,J=2.7,8.1Hz,1H),5.14(s,2H), 3.83(s,3H),3.74(m,2H),3.49(t,J=7.2Hz,2H),3.02(t,J=6.9Hz,2H),2.36(s,3H), 2.29(s,3H),2.22(m,2H),2.20(s,3H),1.77(m,2H),0.94(t,J=7.2Hz,3H).
实施例2(141)
8-(N-丙基-N-(2-甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.18-7.30(m,4H),7.13(d,J=8.1Hz,1H),6.90(d, J=2.4Hz,1H),6.83(dd,J=2.4,8.1Hz,1H),5.13(s,2H),3.83(s,3H),3.78(m,2H), 3.49(t,J=6.9Hz,2H),3.00(t,J=6.9Hz,2H),2.28(s,3H),2.24(s,3H),2.21(m,2H), 2.19(s,3H),1.79(m,2H),0.94(t,J=7.2Hz,3H).
实施例2(142)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-乙氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.7Hz,1H),7.06(d,J=2.4Hz,1H), 6.95(dd,J=2.4,8.7Hz,1H),4.07(m,2H),3.99(m,1H),3.34-3.65(m,2H),3.13(t, J=7.8Hz,2H),2.35(s,3H),2.29(m,2H),1.62-1.93(m,4H),1.42(t,J=6.9Hz,3H), 1.06(t,J=7.5Hz,3H),1.05(t,J=7.2Hz,3H).
实施例2(143)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-乙氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.52(brd,J=10.2Hz,1H),7.32(d,J=8.4Hz,1H), 7.07(d,J=2.4Hz,1H),6.95(dd,J=2.4,8.4Hz,1H),5.49(d,J=16.5Hz,1H),5.39(d, J=16.5Hz,1H),5.28(brs,2H),4.07(m,2H),3.40(m,1H),2.40(s,3H),1.68- 1.98(m,4H),1.43(t,J=6.9Hz,3H),1.07(t,J=7.2Hz,3H),1.06(t,J=7.2Hz,3H).
实施例2(144)
8-(N-甲基-N-己基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.09(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.4Hz,1H), 6.82(dd,J=8.4,2.4Hz,1H),4.01-3.95(m,2H),3.83(s,3H),3.51(s,3H),3.51- 3.42(m,2H),3.18-3.06(m,2H),2.26(s,3H),2.26-2.18(m,2H),2.18(s,3H),1.96- 1.80(m,2H),1.44-1.25(m,6H),0.90(brt,J=6.6Hz,3H).
实施例2(145)
8-(N-甲基-N-(3-戊基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(m,1H),4.55(m,1H),3.83(s,3H),3.46(t,J=7.8Hz,2H),3.27(s,3H),3.10(t, J=6.9Hz,2H),2.26(s,3H),2.45(m,2H),2.19(s,3H),1.76-1.98(m,4H),1.01(t, J=7.2Hz,6H).
实施例2(146)
8-(N-甲基-N-(4-庚基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=3.0Hz,1H), 6.82(dd,J=3.0,8.4Hz,1H),4.80(m,1H),3.83(s,3H),3.47(t,J=7.5Hz,2H), 3.27(s,3H),3.09(t,J=7.5Hz,2H),2.25(s,3H),2.24(m,2H),2.19(s,3H),1.64- 1.94(m,4H),1.28-1.58(m,4H),0.97(t,J=7.2Hz,6H).
实施例2(147)
8-(N-环丙基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.54(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.4Hz,1H),7.11(d,J=7.8Hz,2H), 7.09(d,J=2.4Hz,1H),7.02(d,J=7.8Hz,2H),6.94(dd,J=2.4,8.4Hz,1H),5.18- 5.30(m,4H),5.15(s,2H),3.85(s,3H),2.67(m,1H),2.41(s,3H),2.33(s,3H), 0.85-1.00(m,4H).
实施例2(148)
8-(N-环丙基甲基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.58(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=8.4Hz,1H),7.19(d,J=8.1Hz,2H), 7.17(d,J=8.1Hz,2H),7.08(d,J=2.7Hz,1H),6.96(dd,J=2.7,8.4Hz,1H),5.10- 5.50(m,6H),3.85(s,3H),3.69(m,2H),2.37(s,3H),2.36(s,3H),1.21(m,1H), 0.65(m,2H),0.22(m,2H).
实施例2(149)
8-(N-环丁基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.45(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.17(,d J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.78(dd,J=8.1,2.7Hz,1H),4.35(quint,J=7.5Hz,1H),3.82(s,3H),3.69-3.10(m, 2H),2.94(t,J=6.9Hz,2H),2.90(t,J=7.8Hz,2H),2.33(s,3H),2.22-2.02(m,9H), 1.78-1.58(m,2H),1.39(sext,J=7.8Hz,2H),0.84(t,J=7.8Hz,3H).
实施例2(150)
8-(N-iso丁基-N-(2-二甲氨基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.63(乙酸乙酯∶乙酸∶水=3∶1∶1);
NMR(300MHz,DMSO-d6):δ7.11(d,J=8.4Hz,1H),6.91(d,J=2.7Hz,1H), 6.82(dd,J=8.4,2.7Hz,1H),4.08-3.98(m,2H),3.78(s,3H),3.50-3.42(m,2H), 3.42-3.32(m,2H),3.01(brt,J=6.9Hz,2H),2.87(brt,J=7.8Hz,2H),2.79(s,3H), 2.77(s,3H),2.25(s,3H),2.18-2.00(m,2H),2.08(s,3H),1.80-1.64(m,1H),0.83(d, J=6.6Hz,6H).
实施例2(151)
8-(N-丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.34(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.7Hz,1H),7.28-7.24(m,2H),7.08(d, J=3.0Hz,1H),7.05-6.97(m,2H),6.90(dd,J=8.7,3.0Hz,1H),5.09(s,2H),4.91(s, 2H),4.89(s,2H),3.84(s,3H),3.33-3.27(m,2H),2.40(s,3H),1.63(sext,J=7.8Hz, 2H),0.39(t,J=7.8Hz,3H).
实施例2(152)
8-(N-丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.36(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.28-7.20(m,2H),7.07(d, J=2.7Hz,1H),7.02-6.94(m,2H),6.89(dd,J=8.4,2.7Hz,1H),4.80(s,2H),3.84(s, 3H),3.36(brt,J=7.5Hz,2H),2.90(t,J=7.5Hz,2H),2.82(t,J=7.5Hz,2H),2.39(s, 3H),2.07(quint,J=7.5Hz,2H),1.68-1.48(m,2H),0.87(t,J=7.5Hz,3H).
实施例2(153)
8-(N-环丙基甲基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.67(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=8.4Hz,1H),7.27(d,J=8.4Hz,2H), 7.22(d,J=8.4Hz,2H),7.09(d,J=2.7Hz,1H),6.97(dd,J=2.7,8.4Hz,1H),5.48(d, J=16.5Hz,1H),5.37(d,J=16.5Hz,1H),5.33(d,J=15.9Hz,1H),5.24(s,2H), 5.24(d,J=15.9Hz,1H),3.85(s,3H),3.69(m,2H),2.50(s,3H),2.36(s,3H), 1.19(m,1H),0.69(m,2H),0.24(m,2H).
实施例2(154)
8-(N,N-二丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4- d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.69(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.33(d,J=8.7Hz,1H),7.08(d,J=2.4Hz,1H), 6.96(dd,J=2.4,8.7Hz,1H),5.48(td,J=1.8,16.8Hz,1H),5.36(td,J=1.8,16.8Hz, 1H),5.21(t,J=1.8Hz,2H),3.85(m,4H),3.85(s,3H),2.35(s,3H),1.83(m,4H), 1.02(t,J=7.2Hz,6H).
实施例2(155)
8-(N,N-二丁氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4- d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.74(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.96(dd,J=2.4,8.4Hz,1H),5.47(d,J=16.5Hz,1H),5.36(d,J=16.5Hz,1H),5.21(s, 2H),3.88(m,4H),3.85(s,3H),2.34(s,3H),1.79(m,4H),1.42(m,4H),1.00(t, J=7.2Hz,6H).
实施例2(156)
8-(N-环丙基甲基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.27(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.33-7.26(m,3H),7.06(d,J=2.7Hz,1H),7.01- 6.95(m,2H),6.88(dd,J=8.4,2.7Hz,1H),4.88(s,2H),3.84(s,3H),3.38(d, J=6.9Hz,2H),2.96(t,J=7.2Hz,2H),2.91(t,J=7.2Hz,2H),2.39(s,3H), 2.10(quint,J=7.2Hz,2H),1.10-0.98(m,1H),0.49-0.42(m,2H),0.08-0.02(m, 2H).
实施例2(157)
8-(N-丙基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf 0.43(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33(d,J=8.7Hz,1H),7.19(d,J=8.1Hz,2H), 7.13(d,J=8.1Hz,2H),7.08(d,J=2.7Hz,1H),6.95(dd,J=2.7,8.1Hz,1H),5.28(m, 2H),5.13(m,2H),5.08(m,2H),3.85(s,3H),3.64(m,2H),2.37(s,3H),2.36(s, 3H),1.80(m,2H),0.95(t,J=7.5Hz,3H).
实施例2(158)
8-(3-戊氨基)-2-甲基-3-(3-氯-5-三氟甲基吡啶-2-基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.19(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.91(s,1H),8.12(s,1H),3.99(m,1H),3.50(m, 2H),3.15(m,2H),2.47(s,3H),2.32(m,2H),1.94-1.64(m,4H),1.06(brt,J=6.9Hz, 6H).
实施例2(159)
8-(N-丁基-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.21(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.1Hz,1H),7.08(d,J=2.4Hz,1H), 6.96(dd,J=8.1,2.4Hz,1H),5.47 and 5.35(ABd,J=16.5Hz,2H),5.21(brs,2H), 4.00-3.75(m)and 3.85(s)total 7H,2.34(s,3H),1.90-1.75(m,4H),1.42(sext, J=7.2Hz,2H),1.05-0.98(m,6H).
实施例2(160)
8-(N-丁基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.33(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.12(d,J=8.7Hz,1H),6.89(d,J=2.4Hz,1H), 6.82(dd,J=8.7,2.4Hz,1H),3.95-3.80(m)and 3.83(s)total 7H,3.48(t,J=7.5Hz, 2H),3.02(t,J=7.5Hz,2H),2.30-2.18(m)and 2.27(s)total 5H,2.19(s,3H),1.80- 1.65(m,4H),1.38(sext,J=7.2Hz,2H),0.96(t,J=7.2Hz,6H).
实施例2(161)
8-(4-庚氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.52(d,J=10.2Hz,1H),7.34(d,J=8.7Hz,1H), 7.08(d,J=2.4Hz,1H),6.97(dd,J=2.4,8.7Hz,1H),5.49(brd.J=16.8Hz,1H), 5.39(d,J=16.8Hz,1H),5.28(m,2H),3.85(s,3H),3.53(m,1H),2.39(s,3H), 1.75(m,4H),1.47(m,4H),1.00(t,J=7.2Hz,6H).
实施例2(162)
8-(N-丁基-N-乙基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33(d,J=8.7Hz,1H),7.08(d,J=2.4Hz,1H), 6.96(dd,J=2.4,8.7Hz,1H),5.46(m,1H),5.35(m,1H),5.23(t,J=1.5Hz,2H), 3.80-4.00(m,4H),3.85(s,3H),2.34(s,3H),1.80(m,2H),1.46(t,J=7.2Hz,3H), 1.44(m,2H),1.01(t,J=7.2Hz,3H).
实施例2(163)
8-(N-环丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.80(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.17-7.09(m,2H),7.07(d, J=2.7Hz,1H),6.96-6.93(m,2H),6.90(dd,J=8.4,2.7Hz,1H),5.01(s,2H),3.84(s, 3H),2.97-2.86(m,4H),2.75(m,1H),2.39(s,3H),2.03(m,2H),0.80-0.68(m,4H).
实施例2(164)
8-(N-丙基-N-(2-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.85(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.24-7.12(m,2H),7.19(d,J=8.1Hz,1H),7.06- 6.97(m,2H),6.87(d,J=2.7Hz,1H),6.80(dd,J=8.1,2.7Hz,1H),5.00-4.92(m,2H), 3.83(s,3H),3.42-3.36(m,2H),2.86(t,J=7.5Hz,2H),2.75(t,J=7.5Hz,2H), 2.37(s,3H),2.19(s,3H),2.02(quint,J=7.5Hz,2H),1.68-1.46(m,2H),0.90(t, J=7.2Hz,3H).
实施例2(165)
8-(N-丙基-N-(3-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.86(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30-7.22(m,1H),7.18(d,J=8.4Hz,1H),7.08- 7.01(m,2H),6.98-6.90(m,1H),6.87(d,J=2.4Hz,1H),6.80(dd,J=8.4,2.4Hz,1H), 4.85(s,2H),3.83(s,3H),3.42-3.36(m,2H),2.89(t,J=7.5Hz,2H),2.86(t,J=7.5Hz, 2H),2.36(s,3H),2.19(s,3H),2.09(quint,J=7.5Hz,2H),1.68-1.52(m,2H),0.88(t, J=7.5Hz,3H).
实施例2(166)
8-二环丙基甲基氨基-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.39(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.06(d,J=2.4Hz,1H), 6.89(dd,J=2.4,8.7Hz,1H),6.48(brd,J=9.9Hz,1H),5.22(brs,2H),4.89(brs,2H), 3.83(s,3H),2.87(m,1H),2.37(s,3H),1.15(m,2H),0.61(m,4H),0.42(m,4H).
实施例2(167)
8-二环丙基甲基氨基-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.4Hz,1H),7.04(d,J=2.4Hz,1H), 6.87(dd,J=2.4,8.4Hz,1H),6.37(brd,J=9.9Hz,1H),3.82(s,3H),3.40(m,1H), 3.01(t,J=6.9Hz,2H),2.88(t,J=7.8Hz,2H),2.35(s,3H),2.11(m,2H),1.14(m, 2H),0.50-0.66(m,4H),0.35-0.50(m,4H).
实施例2(168)
8-(N-丁基-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.40-7.30(m,1H),7.08(s,1H),7.00-6.90(m, 1H),4.00-3.80(m)and 3.85(s)total 7H,3.65-3.30(m,2H),3.10-2.95(m,2H),2.40- 2.20(m)and 2.33(s)total 5H,1.80-1.65(m,4H),1.43-1.30(m,2H),0.97(t,J=6.6Hz, 6H).
实施例2(169)
8-(N-环丙基甲基-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.4Hz,1H),7.05(d,J=2.7Hz,1H), 6.88(dd,J=8.4,2.7Hz,1H),3.83(s,3H),3.64-3.58(m,2H),3.53(d,J=6.9Hz,2H), 3.01(t,J=7.2Hz,2H),2.92(t,J=7.2Hz,2H),2.36(s,3H),2.14(quint,J=7.2Hz,2H), 1.65-1.55(m,2H),1.05-0.90(m,1H),0.91(t,J=7.5Hz,3H),0.50-0.40(m,2H), 0.15-0.05(m,2H).
实施例2(170)
8-(N-环丙基甲基-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30(d,J=8.4Hz,1H),7.07(d,J=2.7Hz,1H), 6.89(dd,J=8.4,2.7Hz,1H),5.23(s,2H),4.91(s,2H),3.83(s,3H),3.65-3.50(m, 4H),2.38(s,3H),1.63(quint,J=7.2Hz,2H),1.10-0.98(m,1H),0.94(t,J=7.2Hz, 3H),0.56-0.46(m,2H),0.15(dd,J=10.8,5.1Hz,2H).
实施例2(171)
8-(N-(2-丁炔基)-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.44(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.7Hz,1H),7.08(d,J=1.8Hz,1H), 6.96(brd,J=8.7Hz,1H),4.56(d,J=2.1Hz,2H),4.05-3.80(m)and 3.85(s)total 5H, 3.65-3.30(m,2H),3.25-3.10(m,2H),2.40-2.20(m)and 2.33(s)total 5H,1.95- 1.80(m)and 1.89(s)total 5H,1.01(t,J=7.2Hz,3H).
实施例2(172)
8-(N-(2-丁炔基)-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.36(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.7Hz,1H),7.07(d,J=2.7Hz,1H), 6.90(dd,J=8.7,2.7Hz,1H),5.32(s,2H),4.91(s,2H),4.45(q,J=2.1Hz,2H),3.84(s, 3H),3.55-3.45(m,2H),2.38(s,3H),1.82(t,J=2.1Hz,3H),1.72(sext,J=7.2Hz, 2H),0.98(t,J=7.2Hz,3H).
实施例2(173)
8-(N-丁基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.34(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=7.8Hz,1H),7.08(d,J=2.1Hz,1H), 6.97(brd,J=7.8Hz,1H),4.30-4.18(m,2H),3.90-3.78(m)and 3.85(s)total 5H, 3.70-3.30(m)and 3.64(m)total 4H,3.30(s,3H),3.08-2.98(m,2H),2.40- 2.18(m)and 2.33(s)total 5H,1.80-1.65(m,2H),1.43-1.35(m,2H),0.96(t,J=7.2Hz, 3H).
实施例2(174)
8-(N-丁基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.39(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.40-7.30(m,1H),7.08(brs,1H),7.05-6.95(m, 1H),5.60-5.35(m,2H),5.30-5.15(m,2H),4.40-4.20(m,2H),3.90-3.70(m)and 3.85(s)total 7H,3.35(s,3H),2.35(s,3H),1.85-1.70(m,2H),1.50-1.38(m,2H), 0.99(t,J=6.9Hz,3H).
实施例2(175)
8-(N-丙基-N-(4-三氟甲基氧苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.42(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.39-7.33(m,2H),7.31(d,J=8.4Hz,1H),7.21- 7.15(m,2H),7.08(d,J=2.4Hz,1H),6.91(dd,J=8.4,2.4Hz,1H),5.12(s,2H), 4.95(s,2H),4.90(s,2H),3.84(s,3H),3.36-3.28(m,2H),2.40(s,3H),1.70-1.54(m, 2H),0.89(t,J=7.5Hz,3H).
实施例2(176)
8-(N-环丙基甲基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.28(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.33-7.26(m,2H),7.18(d,J=8.4Hz,1H),7.03- 6.94(m,2H),6.87(d,J=2.7Hz,1H),6.80(dd,J=8.4,2.7Hz,1H),4.88(s,2H), 3.83(s,3H),3.38(d,J=6.9Hz,2H),2.95(t,J=6.9Hz,2H),2.89(t,J=6.9Hz,2H), 2.36(s,3H),2.19(s,3H),2.09(quint,J=6.9Hz,2H),1.01(m,1H),0.58-0.42(m, 2H),0.20-0.01(m,2H).
实施例2(177)
8-(3-戊氨基)-2-甲基-3-(3,5-二氯吡啶-2-基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.38(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.58(d,J=2.1Hz,1H),7.81(d,J=2.1Hz,1H), 6.24(brd,J=11.1Hz,1H),3.80(m,1H),3.08(t,J=7.5Hz,2H),2.93(t,J=7.5Hz,2H), 2.41(s,3H),2.15(quint,J=7.5Hz,2H),1.80-1.52(m,4H),1.00(t,J=7.5Hz,6H).
实施例2(178)
8-(N-丁基-N-乙基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=8.4Hz,1H),7,07(d,J=2.7Hz,1H), 6.96(dd,J=2.7,8.4Hz,1H),3.94(m,4H),3.85(s,3H),3.30-3.62(m,2H),3.05(m, 2H),2.32(s,3H),2.25(m,2H),1.74(m,2H),1.32-1.48(m,5H),0.98(t,J=7.8Hz, 3H).
实施例2(179)
8-(N-环丙基甲基-N-(4-三氟甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧 基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.65(d,J=8.4Hz,2H),7.47(d,J=8.4Hz,2H), 7.13(d,J=8.7Hz,1H),6.90(d,J=2.4Hz,1H),6.83(dd,J=2.4,8.7Hz,1H),5.37(s, 2H),3.83(s,3H),3.66(m,2H),3.52(t,J=7.5Hz,2H),3.11(t,J=7.2Hz,2H),2.29(s, 3H),2.27(m,2H),2.19(s,3H),1.14(m,1H),0.65(m,2H),0.17(m,2H).
实施例2(180)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.52(brd,J=10.2Hz,1H),7.35(d,J=8.7Hz,1H), 7.08(d,J=2.7Hz,1H),6.96(dd,J=2.7,8.7Hz,1H),5.50(d,J=16.5Hz,1H),5.39(d, J=16.5Hz,1H),5.29(s,2H),3.85(s,3H),3.39(m,1H),2.40(s,3H),1.68-1.98(m, 4H),1.06(m,6H).
实施例2(181)
8-(N-环丙基甲氨基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.28(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.34-7.28(m,2H),7.30(d,J=8.4Hz,1H),7.08(d, J=2.7Hz,1H),7.05-6.98(m,2H),6.901(dd,J=8.4,2.7Hz,1H),5.21(s,2H),4.93(s, 2H),4.90(s,2H),3.84(s,3H),3.38(d,J=6.9H z,2H),2.40(s,3H),1.08-0.94(m, 1H),0.56-0.48(m,2H),0.14-0.06(m,2H).
实施例2(182)
8-(N-苄基-N-(2-二甲氨基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.60(乙酸乙酯∶乙酸∶水=3∶1∶1);
NMR(300MHz,CD3OD):δ7.45-7.32(m,5H),7.18(d,J=8.4Hz,1H),6.98(d, J=2.7Hz,1H),6.90(dd,J=8.4,2.7Hz,1H),5.20(s,2H),4.40(m,2H),3.84(s,3H), 3.75(m,2H),3.16(m,2H),3.06(m,2H),2.96(s,6H),2.35(s,3H),2.38-2.18(m, 2H),2.11(s,3H).
实施例2(183)
8-(N-苄基-N-(2-二甲氨基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.80(乙酸乙酯∶乙酸∶水=3∶1∶1);
NMR(300MHz,CD3OD):δ7.60-7.30(m,6H),7.19(d,J=2.4Hz,1H),7.08- 7.02(m,1H),5.13(s,2H),4.96(s,2H),4.94(s,2H),4.40-4.24(m,2H),3.87(s,3H), 3.76(m,1H),3.56(m,1H),2.99(s,3H),2.98(s,3H),2.44(s,3H).
实施例2(184)
8-(N-苄基-N-(2-二甲氨基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶二盐酸
TLC:Rf0.27(氯仿∶甲醇=9∶1);
NMR(300MHz,CD3OD):δ7.46-7.26(m,6H),7.20(d,J=2.1Hz,1H),7.08- 7.02(m,1H),5.11(brs,2H),4.34-4.20(m,2H),3.87(s,3H),3.76-3.64(m,2H), 3.34-2.86(m)and 2.96(s)total 10H,2.41(s,3H),2.26-2.10(m,2H).
实施例2(185)
8-(N-(2-丁炔基)-N-乙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.36(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.88(d,J=2.7Hz,1H), 6.82(dd,J=2.7,8.4Hz,1H),4.55(q,J=2.1Hz,2H),4.08(m,2H),3.83(s,3H), 3.48(t,J=7.5Hz,2H),3.22(t,J=6.9Hz,2H),2.28(s,3H),2.24(m,2H),2.17(s,3H), 1.90(t,J=2.1Hz,3H),1.47(t,J=7.2Hz,3H).
实施例2(186)
8-(N-(2-丁炔基)-N-乙基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.95(dd,J=2.4,8.4Hz,1H),5.41(s,2H),5.36(m,2H),4.46(m,2H),4.08(m,2H), 3.85(s,3H),2.36(s,3H),1.89(t,J=2.7Hz,3H),1.51(t,J=7.2Hz,3H).
实施例2(187)
8-(N-(2-丁炔基)-N-乙基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.32(己烷∶乙酸乙酯=2∶1);
NMR(300Hz,CDCl3):δ7.34(d,J=8.4Hz,1H),7.07(d,J=2.7Hz,1H), 6.96(dd,J=2.7,8.4Hz,1H),4.54(m,2H),4.09(m,2H),3.85(s,3H),3.35-3.64(m, 2H),3.22(t,J=7.2Hz,2H),2.34(S,3H),2.26(m,2H),1.90(t,J=2.4Hz,3H),1.47(t, J=7.2Hz,3H).
实施例2(188)
8-(N,N-二丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.40(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.30(d,J=8.4Hz,1H),7.05(d,J=2.7Hz,1H), 6.88(dd,J=2.7,8.4Hz,1H),3.83(s,3H),3.56(m,4H),2.95(t,J=7.2Hz,2H), 2.91(t,J=8.1Hz,2H),2.36(s,3H),2.13(m,2H),1.58(m,4H),0.89(t,J=7.2Hz, 6H).
实施例2(189)
8-(N-(2-丁炔基)-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.50(甲苯∶丙酮=5∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.4Hz,1H),7.07(d,J=2.7Hz,1H), 6.90(dd,J=8.4,2.7Hz,1H),5.35(s,2H),4.91(s,2H),4.56(m,2H),3.83(s,3H), 3.50(m,2H),2.39(s,3H),1.82(t,J=2.4Hz,3H),1.15(m,1H),0.64-0.56(m,2H), 0.38-0.28(m,2H).
实施例2(190)
8-(N-丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.22(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.60(brd,J=8.1Hz,2H),7.47(brd,J=8.1Hz,2H), 7.17(d,J=8.7Hz,1H),6.87(d,J=2.7Hz,1H),6.79(dd,J=8.7,2.7Hz,1H),4.90(s, 2H),3.83(s,3H),3.39(m,2H),2.94-2.82(m,4H),2.34(s,3H),2.18(s,3H), 2.11(m,2H),1.59(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(191)
8-(N-环丙基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.20(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.19-7.13(m,2H),7.08(d, J=2.7Hz,1H),7.06-7.01(m,2H),6.91(dd,J=8.4,2.7Hz,1H),5.20(s,2H),5.15(s, 2H),4.91(s,2H),3.84(s,3H),2.56(m,1H),2.46(s,3H),2.41(s,3H),0.95-0.88(m, 4H).
实施例2(192)
8-(N-丙基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.25(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.7Hz,1H),7.20(s,4H),7.08(d, J=2.7Hz,1H),6.90(dd,J=8.7,2.7Hz,1H),5.10(s,2H),4.90(s,2H),4.89(s,2H), 3.84(s,3H),3.34(m,2H),2.48(s,3H),2.40(s,3H),1.70-1.50(m,2H),0.89(t, J=7.5Hz,3H).
实施例2(193)
8-(N-环丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.19(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.14-7.04(m,3H),7.02- 6.94(m,2H),6.92(dd,J=8.4,2.4Hz,1H),5.19(s,2H),5.16(s,2H),4.91(s,2H), 3.84(s,3H),2.55(m,1H),2.41(s,3H),0.90-0.76(m,4H).
实施例2(194)
8-(N-丙基-N-(3-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.33(d,J=8.4Hz,1H),7.26-7.15(m,2H),7.07(d, J=2.4Hz,1H),7.05-6.98(m,2H),6.89(dd,J=8.4,2.4Hz,1H),4.94(s,2H),3.84(s, 3H),3.39(m,2H),2.88(t,J=7.5Hz,2H),2.77(t,J=7.5Hz,2H),2.40(s,3H), 2.04(quint,J=7.5Hz,2H),1.63(m,2H),0.90(t,J=7.5Hz,3H).
实施例2(195)
8-(N-丙基-N-(3-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.46(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.28-7.16(m,2H),7.08(d, J=2.4Hz,1H),7.07-6.99(m,2H),6.91(dd,J=8.4,2.4Hz,1H),5.07(s,2H),5.04(s, 2H),4.88(s,2H),3.84(s,3H),3.13(m,2H),2.41(s,3H),1.68(sext,J=7.5Hz,2H), 0.93(t,J=7.5Hz,3H).
实施例2(196)
8-二丙氨基-2-甲基-3-(2,5-二氯苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
TLC:Rf0.64(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.41(d,J=8.7Hz,1H),7.40(d,J=2.4Hz,1H), 7.23(dd,J=8.7,2.4Hz,1H),3.60-3.52(m,4H),2.96(t,J=7.8Hz)and 2.93(t, J=7.8Hz)total 4H,237(s,3H),2.15(quint,J=7.8Hz,2H),1.65-1.50(m,4H), 0.89(t,J=7.2Hz,6H).
实施例2(197)
8-二丙氨基-2-甲基-3-(2,4-二氯苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
TLC:Rf0.57(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.51(d,J=2.4Hz,1H),7.35(d,J=8.1Hz,1H), 7.29(dd,J=8.1,2.4Hz,1H),3.65-3.50(m,4H),2.96(t,J=7.2Hz)and 2.92(t, J=7.2Hz)total 4H,2.36(s,3H),2.14(quint,J=7.2Hz,2H),1.63-1.45(m,4H), 0.89(t,J=7.5Hz,6H).
实施例2(198)
8-二丙氨基-2-甲基-3-(4-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧 啶
TLC:Rf0.58(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.58(d,J=7.8Hz,2H),7.24(d,J=7.8Hz,2H), 3.60-3.52(m,4H),3.00-2.90(m,4H),2.56(s,3H),2.37(s,3H),2.14(quint, J=7.5Hz,2H),1.64-1.48(m,4H),0.87(t,J=7.2Hz,6H).
实施例2(199)
8-二丙氨基-2-甲基-3-(3-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧 啶
TLC:Rf0.61(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.50(s)and 7.47(d,J=7.5Hz)total 2H,7.32(t, J=7.5Hz,1H),7.06(t,J=7.5Hz,1H),3.60-3.52(m,4H),2.96(t,J=7.8Hz,4H), 2.57(s,3H),2.41(s,3H),2.15(quint,J=7.8Hz,2H),1.64-1.45(m,4H),0.88(t, J=7.2Hz,6H).
实施例2(200)
8-二丙氨基-2-甲基-3-(2-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧 啶
TLC:Rf0.56(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.35-7.20(m,4H),3.62-3.54(m,4H),2.96(t, J=7.2Hz)and 2.90(t,J=7.2Hz)total 4H,2.34(s,3H),2.22(s,3H),2.13(quint, J=7.2Hz,2H),1.63-1.50(m,4H),0.89(t,J=7.5Hz,6H).
实施例2(201)
8-(N-丙基-N-(苯并[d]1,3-二氧戊环-5-基)甲氨基)-2-甲基-3-(2-甲基-4-甲 氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.31(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.18(d,J=8.1Hz,1H),6.87(d,J=2.7Hz,1H), 6.77-6.83(m,2H),6.67-6.75(m,2H),5.94(s,2H),4.74(s,2H),3.83(s,3H), 3.37(m,2H),2.89(t,J=7.8Hz,2H),2.85(t,J=7.5Hz,2H),2.35(s,3H),2.20(s,3H), 2.08(m,2H),1.58(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(202)
8-(N-丙基-N-(苯并[d]1,3-二氧戊环-5-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧 基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.38(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.36(d,J=8.4Hz,1H),7.08(d,J=2.7Hz,1H), 6.97(dd,J=8.4,2.7Hz,1H),6.70-6.82(m,3H),6.00(s,2H),5.07(s,2H),3.85(s, 3H),3.71(m,2H),3.36-3.64(m,2H),3.03(t,J=7.4Hz,2H),2.35(s,3H),2.24(m, 2H),1.74(m,2H),0.93(t,J=7.5Hz,3H).
实施例2(203)
8-(3-戊氨基)-2-甲基-3-(2-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
TLC:Rf0.39(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.30-7.18(m,4H),6.23(d,J=10.5Hz,1H),3.90- 3.75(m,1H),3.09(t,J=7.2Hz,2H),2.90(t,J=7.2Hz,2H),2.32(s,3H),2.22(s,3H), 2.14(quint,J=7.2Hz,2H),1.80-1.58(m,4H),1.08-0.96(m,6H).
实施例2(204)
8-(3-戊氨基)-2-甲基-3-(3-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
TLC:Rf0.45(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.50(s,1H),7.46(d,J=7.8Hz,1H),7.31(t, J=7.8Hz,1H),7.05(d,J=7.8Hz,1H),6.21(d,J=10.8Hz,1H),3.86-3.74(m,1H), 3.08(t,J=7.2Hz,2H),2.95(t,J=7.2Hz,2H),2.55(s,3H),2.41(s,3H),2.15(quint, J=7.2Hz,2H),1.82-1.55(m,4H),1.01(t,J=7.5Hz,6H).
实施例2(205)
8-(3-戊氨基)-2-甲基-3-(4-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
TLC:Rf0.47(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.57(d,J=7.8Hz,2H),7.24(d,J=7.8Hz,2H), 6.20(10.5Hz,1H),3.83-3.75(m,1H),3.08(t,J=7.2Hz,2H),2.94(t,J=7.2Hz,2H), 2.55(s,3H),2.37(s,3H),2.15(quint,J=7.2Hz,2H),1.80-1.52(m,4H),1.00(t, J=7.2Hz,6H).
实施例2(206)
8-(3-戊氨基)-2-甲基-3-(2-甲基硫-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.10(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.26-7.16(m,1H),6.83(m,1H),6.84-6.76(m, 1H),3.97(m,1H),3.86(s,3H),3.48(m,2H),3.12(m,2H),2.44(s,3H),2.33(s, 3H),2.28(m,2H),1.95-1.44(m,4H),1.11-0.99(m,6H).
实施例2(207)
8-(N-丙基-N-(苯并[d]1,3-二氧戊环-5-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧 基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.7Hz,1H),7.08(d,J=2.7Hz,1H), 6.95(dd,J=2.7,8.7Hz,1H),6.78-6.83(m,2H),6.72(m,1H),5.99(s,2H),5.28(m, 2H),5.16(s,2H),5.04(m,2H),3.85(s,3H),3.60(m,2H),2.38(s,3H),1.77(m, 2H),0.95(t,J=7.2Hz,3H).
实施例2(208)
8-(N-苄基-N-环丙基甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.58(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.25-7.43(m,5H),7.13(d,J=7.8Hz,1H),6.90(d, J=2.4Hz,1H),6.83(dd,J=2.4,7.8Hz,1H),5.28(s,2H),3.84(s,3H),3.69(m,2H), 3.48(t,J=8.1Hz,2H),3.07(t,J=7.2Hz,2H),2.30(s,3H),2.24(m,2H),2.19(s,3H), 1.16(m,1H),0.63(m,2H),0.18(m,2H).
实施例2(209)
8-(N-苄基-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.56(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.25-7.43(m,6H),7.09(d,J=2.7Hz,1H), 6.96(dd,J=2.7,8.4Hz,1H),5.27(m,2H),3.85(s,3H),3.68(m,2H),3.48(m,2H), 3.07(t,J=6.9Hz,2H),2.35(s,3H),2.23(m,2H),1.16(m,1H),0.64(m,2H), 0.18(m,2H).
实施例2(210)
8-(N-苄基-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.26-7.45(m,6H),7.09(d,J=2.4Hz,1H), 6.96(dd,J=2.4,8.1Hz,1H),5.36(m,2H),5.28(m,2H),5.23(s,2H),3.85(s,3H), 3.69(m,2H),2.37(s,3H),1.21(m,1H),0.66(m,2H),0.22(m,2H).
实施例2(211)
8-(N-丁基-N-(2-丁炔基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.38(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),4.40(brs,2H),3.82(s,3H),3.59(m,2H),3.11(t, J=7.2Hz,2H),2.91(t,J=7.8Hz,2H),2.32(s,3H),2.18(s,3H),2.13(m,2H),1.81(t, J=2.1Hz,3H),1.63(m,2H),1.38(m,2H),0.94(t,J=7.5Hz,3H).
实施例2(212)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-氟苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.44(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,DMSO-d6):δ7.34-7.24(m,2H),7.20-7.10(m,1H),4.03- 3.85(m,1H),3.14(brt,J=8.1Hz,2H),2.95(brt,J=8.1Hz,2H),2.25(s,3H),2.25- 2.10(m)and 2.12(s)total 5H,1.85-1.60(m,4H),0.95-0.85(m,6H).
实施例2(213)
8-(3-戊氨基)-2-甲基-3-(2,5-二氯苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶盐酸
TLC:Rf0.46(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,DMSO-d6):δ7.68(d,J=8.4Hz,1H),7.62-7.55(m)and 7.59(s)total 2H,4.03-3.85(m,1H),3.14(brt,J=7.8Hz,2H),2.96(brt,J=7.8Hz,2H), 2.32(s,3H),2.25-2.10(m,2H),1.85-1.60(m,4H),0.89(t,J=7.5Hz,6H).
实施例2(214)
8-(3-戊氨基)-2-甲基-3-(2,4-二甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.43(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,DMSO-d6):δ7.24(d,J=8.1Hz,1H),6.71(d,J=2.4Hz,1H), 6.66(dd,J=8.1,2.4Hz,1H),4.05-3.85(m,1H),3.85(s,3H),3.74(s,H),3.15(brt, J=8.1Hz,2H),2.99(brt,J=8.1Hz,2H),2.33(s,3H),2.25-2.10(m,2H),1.85- 1.63(m,4H),0.89(t,J=7.5Hz,6H).
实施例2(215)
8-(3-戊氨基)-2-甲基-3-(2-氟-4-甲基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.43(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,DMSO-d6):δ9.20-9.00(m,1H),7.39(t,J=7.8Hz,1H), 7.22(d,J=11.1Hz,1H),7.17(d,J=7.8Hz,1H),4.05-3.60(m,1H,covered with H2O in DMSO-d6),3.14(brt,J=7.8Hz,2H),2.99(brt,J=7.8Hz,2H),2.40(s,3H), 2.37(s,3H),2.18(quint,J=7.8Hz,2H),1.83-1.60(m,4H),0.89(t,J=7.5Hz,6H).
实施例2(216)
8-(N-丁基-N-(2-丁炔基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.80(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.06(d,J=2.4Hz,1H), 6.88(dd,J=8.7,2.4Hz,1H),4.39(q,J=2.1Hz,2H),3.83(s,3H),3.59(m,2H), 3.11(t,J=7.5Hz,2H),2.93(t,J=7.5Hz,2H),2.36(s,3H),2.14(quint,J=7.5Hz, 2H),1.81(t,J=2.1Hz,3H),1.68-1.54(m,2H),1.39(sext,J=7.5Hz,2H),0.94(t, J=7.5Hz,3H).
实施例2(217)
8-(N-丁基-N-(2-丁炔基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.78(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.7Hz,1H),7.07(d,J=2.7Hz,1H), 6.89(dd,J=8.7,2.7Hz,1H),5.33(s,2H),4.91(s,2H),4.44(q,J=2.4Hz,2H),3.83(s, 3H),3.54(m,2H),2.38(s,3H),1.82(t,J=2.4Hz,3H),1.74-1.61(m,2H),1.41(sext, J=7.5Hz,2H),0.96(t,J=7.5Hz,3H).
实施例2(218)
8-(3-甲基-2-丁氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.36(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.45(brd,J=10.2Hz,1H),7.11(dd J=4.2,8.4Hz, 1H),6.89(d,J=2.4Hz,1H),6.82(dd,J=2.4,8.4Hz,1H),4.07(m,1H),3.83(s,3H), 3.49(m,2H),3.15(t,J=6.9Hz,2H),2.29(m,2H),2.28(s,3H),2.20 and 2.19(s, total 3H),1.99(m,1H),1.42 and 1.41(d,J=6.6Hz,total 3H),1.05-1.14(m,6H).
实施例2(219)
8-(1-cyclo己基乙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.36(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.42(brd,J=10.5Hz,1H),7.11 and 7.10(d, J=8.1Hz,total 1H),6.88(d,J=2.7Hz,1H),6.81(dd,J=2.7,8.1Hz,1H),4.03(m, 1H),3.82(s,3H),3.48(m,2H),3.12(t,J=7.5Hz,2H),2.28(m,2H),2.28(s,3H), 2.20 and 2.18(s,total 3H),1.52-1.95(m,6H),1.41 and 1.40(d,J=6.6Hz,total 3H), 1.01-1.37(m,5H).
实施例2(220)
8-(2-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.36(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.34(brd,J=9.6Hz,1H),7.11 and 7.10(d, J=8.7Hz,total 1H),6.89(d,J=2.7Hz,1H),6.81(dd,J=2.7,8.7Hz,1H),4.25(m, 1H),3.83(s,3H),3.49(m,2H),3.16(t,J=6.9Hz,2H),2.29(m,2H),2.28(s,3H), 2.20 and 2.19(s,total 3H),1.70-1.80(m,2H),1.44-1.58(m,2H),1.47 and 1.46(d, J=6.6Hz,total 3H),1.01(m,3H).
实施例2(221)
8-(2-庚氨基)-2-甲基-3-(2-甲基4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶盐酸
TLC:Rf0.43(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(brd,J=10.2Hz,1H),7.12 and 7.11(d, J=8.4Hz,total 1H),6.89(d,J=2.7Hz,1H),6.82(dd,J=2.7,8.4Hz,1H),4.22(m, 1H),3.83(s,3H),3.50(m,2H),3.15(t,J=6.9Hz,2H),2.29(m,2H),2.28(s,3H), 2.20 and 2.19(s,total 3H),1.71-1.81(m,2H),1.30-1.55(m,9H),0.92(m,3H).
实施例2(222)
8-(1-甲氧基-2-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.30(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.66(brd,J=8.4Hz,1H),7.11 and 7.10(d, J=8.7Hz,total 1H),6.88(d,J=2.7Hz,1H),6.80(dd,J=2.7,8.7Hz,1H),4.46(m, 1H),3.82(s,3H),3.64(dd,J=3.9,9.9Hz,1H),3.42-3.58(m,3H),3.46 and 3.45(s, total 3H),3.23(m,1H),3.11(m,1H),2.29(m,2H),2.29(s,3H),2.19 and 2.18(s, total,3H),1.49(d,J=6.6Hz,3H).
实施例2(223)
8-(2-octyl氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.60(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33(brd,J=10.2Hz,1H),7.12 and 7.11(d, J=8.1Hz,total 1H),6.89(d,J=2.7Hz,1H),6.82(dd,J=2.7,8.1Hz,1H),4.23(m, 1H),3.83(s,3H),3.50(brt,J=7.2Hz,2H),3.15(t,J=6.6Hz,2H),2.29(m,2H), 2.28(s,3H),2.20 and 2.19(s,total 3H),1.75(m,2H),1.46 and 1.45(d,J=6.3Hz, total 3H),1.26-1.45(m,8H),0.90(m,3H).
实施例2(224)
8-(1,2,3,4-四氢萘-1-基)氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.16(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.44(m,1H),7.27-7.14(m,4H),6.85(d,J=2.7Hz, 1H),6.78(dd,J=8.1,2.7Hz,1H),6.69(brd,J=9.9Hz,1H),5.22(m,1H),3.82(s, 3H),3.24-3.08(m,2H),3.00-2.76(m,4H),2.26(s,3H),2.24-1.82(m,6H),2.20(s, 3H).
实施例2(225)
8-((1S,2S,3S,5R)-2,6,6-tri甲基双环[3.1.1]-3-庚基)氨基-2-甲基-3-(2-甲 基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.25(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1Hz,1H),6.85(d,J=2.4Hz,1H), 6.78(dd,J=8.1,2.4Hz,1H),6.35(brd,J=10.8Hz,1H),4.31(m,1H),3.82(s,3H), 3.22-3.06(m,2H),2.91(t,J=8.1Hz,2H),2.62-2.46(m,2H),2.31(s,3H),2.19(s, 3H),2.19-1.82(m,6H),1.29(s,3H),1.20(d,J=6.0Hz,3H),1.11-1.08(m,1H), 1.09(s,3H).
实施例2(226)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-氯苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.41(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.38-7.32(m,2H),7.26-7.10(m,2H),4.04- 3.90(m,1H),3.60-3.30(m,2H),3.13(t,J=6.6Hz,2H),2.39(s,3H),2.35(s,3H), 2.28(quint,J=6.6Hz,2H),1.92-1.40(m,4H),1.06(t,J=7.2Hz,6H).
实施例2(227)
8-(3-戊氨基)-2-甲基-3-(2,5-二甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.52(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.32-7.24(m,1H),7.00-6.90(m,2H),6.85(d, J=2.4Hz,1H),4.05-3.95(m,1H),3.90(s,3H),3.84(s,3H),3.56(t,J=7.8Hz,2H), 3.12(t,J=7.8Hz,2H),2.43(s,3H),2.29(quint,J=7.8Hz,2H),1.90-1.40(m,4H), 1.05(t,J=7.5Hz,6H).
实施例2(228)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶盐酸
TLC:Rf0.24(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.41(t,J=8.1Hz,1H),7.34-7.24(m,2H),7.10- 7.02(m,2H),4.03-3.90(m,1H),3.94(s,3H),3.56(t,J=7.5Hz,2H),3.12(t, J=7.5Hz,2H),2.43(s,3H),2.36-2.20(m,2H),1.90-1.40(m,4H),1.05(t,J=7.5Hz, 6H).
实施例2(229)
8-二环丙基甲基氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.87(m,1H),7.11(d,J=8.7Hz,1H),6.89(d, J=2.7Hz,1H),6.82(dd,J=2.7,8.7Hz,1H),5.37(s,2H),5.19(m,2H),3.83(s,3H), 2.90(m,1H),2.36(s,3H),2.20(s,3H),1.26(m,2H),0.66-0.85(m,4H),0.47(m, 4H).
实施例2(230)
8-(N-丁基-N-乙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃 并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.7Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=2.7,8.7Hz,1H),5.40(s,2H),.5.23(s,2H),3.85-4.00(m,4H),3.83(s, 3H),2.29(s,3H),2.19(s,3H),1.82(m,2H),1.46(t,J=6.9Hz,3H),1.44(m,2H), 1.02(t,J=6.9Hz,3H).
实施例2(231)
8-(N-丁基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.89(d,J=2.4Hz,1H), 6.82(dd,J=2.4,8.4Hz,1H),5.40(s,2H),5.21(s,2H),3.87(m,4H),3.83(s,3H), 2.29(s,3H),2.19(s,3H),1.82(m,4H),1.42(m,2H),1.02(t,J=7.2Hz,3H),1.00(t, J=7.2Hz,3H).
实施例2(232)
8-(N,N-二丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.89(d,J=3.0Hz,1H), 6.82(dd,J=3.0,8.4Hz,1H),5.39(brs,2H),5.21(brs,2H),3.85(m,4H),3.83(s, 3H),2.29(s,3H),2.19(s,3H),1.83(m,4H),1.02(t,J=7.2Hz,6H).
实施例2(233)
8-(N-乙基-N-(4-羟基丁基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(己烷∶乙酸乙酯=1∶2);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.87(d,J=3.0Hz,1H), 6.79(dd,J=3.0,8.4Hz,1H),3.87-4.01(m,4H),3.82(s,3H),3.65(t,J=6.0Hz,2H), 3.38(t,J=7.5Hz,2H),3.06(t,J=7.2Hz,2H),2.27(s,3H),2.24(m,2H),2.17(s,3H), 1.86(m,2H),1.61(m,2H),1.38(t,J=7.2Hz,3H).
实施例2(234)
8-双(2-甲氧基乙基)氨基-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃 并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.35(己烷∶乙酸乙酯=1∶2);
NMR(300MHz,CDCl3):δ7.33(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.96(dd,J=2.4,8.4Hz,1H),5.40(m,1H),5.33(m,1H),5.25(m,2H),4.15(m,4H), 3.85(s,3H),3.71(t,J=5.1Hz,4H),3.35(s,6H),2.35(s,3H).
实施例2(235)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基-5-异丙基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.36(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.23(dd,J=8.4,2.1Hz,1H),7.12(d,J=2.1Hz, 1H),6.98(d,J=8.4Hz,1H),4.00-3.85(m)and 3.91(s)total 4H,3.58-3.30(m,2H), 3.11(t,J=6.9Hz,2H),2.92(m,1H),2.43(s,3H),2.35-2.20(m,2H),1.90-1.50(m, 4H),1.26(d,J=6.9Hz,6H),1.04(t,J=7.5Hz,6H).
实施例2(236)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基-5-氟苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.20-6.95(m,4H),4.04-3.80(m)and 3.91(s)total 4H,3.52-3.40(m,2H),3.12(t,J=7.2Hz,2H),2.43(s,3H),2.27(quint,J=7.2Hz, 2H),1.90-1.40(m,4H),1.05(t,J=7.5Hz,6H).
实施例2(237)
8-(N-丁基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-5-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.44-7.20(m,3H),7.14-6.90(m,4H),5.03(brs, 2H),3.85(s,3H),3.62(m,2H),3.29(m,2H),2.96(m,2H),2.37(s,3H),2.19(m, 2H),1.65(m,2H),1.32(m,2H),0.90(m,3H).
实施例2(238)
8-(N-丁基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.20(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.40-7.26(m,3H),7.12(brd,J=7.8Hz,2H), 7.09(d,J=2.1Hz,1H),6.99-6.92(m,1H),5.40(m,2H),5.30-5.08(m,4H),3.85(s, 3H),3.70(m,2H),2.37(s,3H),1.76(m,2H),1.36(m,2H),0.94(t,J=7.5Hz,3H).
实施例2(239)
8-(N-丁基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.28(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.29(m,2H),7.18-7.04(m,3H),6.89(d,J=2.1Hz, 1H),6.85-6.78(m,1H),5.23(m,2H),5.15(m,2H),5.11(m,2H),3.83(s,3H), 3.58(m,2H),2.33(s,3H),2.20(s,3H),1.71(m,2H),1.35(m,2H),0.95-0.84(m, 3H).
实施例2(240)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基-5-氯苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.33(dd,J=9.0,3.0Hz,1H),7.25-7.05(m)and 7.22(d,J=3.0Hz)total 2H,6.98(d,J=9.0Hz,1H),4.03-3.85(m)and 3.93(s)total 4H, 3.55-3.40(m,2H),3.13(t,J=7.2Hz,2H),2.43(s,3H),2.28(quint,J=7.2Hz,2H), 1.90-1.40(m,4H),1.05(t,J=7.5Hz,6H).
实施例2(241)
8-(N-乙基-N-(2-丁酰基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.37(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=2.7,8.4Hz,1H),5.41(s,4H),4.48(m,2H),4.14(m,2H),3.83(s,3H), 2.31(s,3H),2.18(s,3H),1.90(t,J=2.4Hz,3H),1.54(t,J=7.2Hz,3H).
实施例2(242)
8-(N-丙基-N-(2-丁酰基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.1Hz,1H),6.89(d,J=2.7Hz,1H), 6.82(dd,J=2.7,8.1Hz,1H),5.41(m,2H),5.39(m,2H),5.42(m,2H),3.98(m,2H), 3.83(s,3H),2.31(s,3H),2.18(s,3H),1.94(m,2H),1.89(t,J=2.7Hz,3H),1.05(t, J=7.2Hz,3H).
实施例2(243)
8-(N-丙基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.27(d,J=8.4Hz,2H),7.20(d,J=8.4Hz,2H), 7.12(d,J=8.4Hz,1H),6.90(d,J=2.7Hz,1H),6.83(dd,J=2.7,8.4Hz,1H),5.40(s, 2H),5.11-5.26(m,4H),3.84(s,3H),3.70(m,2H),2.50(s,3H),2.31(s,3H),2.20(s, 3H),1.84(m,2H),0.97(t,J=7.2Hz,3H).
实施例2(244)
8-(N-丙基-N-(苯并[d]1,3-二氧戊环-5-基)甲氨基)-2-甲基-3-(2-甲基-4-甲 氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.13(d,J=8.1Hz,1H),6.90(d,J=2.7Hz,1H), 6.83(dd,J=2.7,8.1Hz,1H),6.82(d,J=7.5Hz,1H),6.78(d,J=1.5Hz,1H),6.73(dd, J=1.5,7.5Hz,1H),6.01(s,2H),5.39(s,2H),5.17(s,2H),5.11(m,2H),3.84(s,3H), 3.69(m,2H),2.32(s,3H),2.21(s,3H),1.81(m,2H),0.96(t,J=7.2Hz,3H).
实施例2(245)
8-(N-苄基-N-环丙基甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34-7.46(m,3H),7.26-7.33(m,2H),7.13(d, J=8.7Hz,1H),6.90(d,J=2.7Hz,1H),6.84(dd,J=2.7,8.7Hz,1H),5.42(s,2H), 5.33(m,2H),5.24(s,2H),3.84(s,3H),3.73(m,2H),2.31(s,3H),2.20(s,3H), 1.24(m,1H),0.69(m,2H),0.24(m,2H).
实施例2(246)
8-(N-环丙基甲基-N-(4-三氟甲基苯基)甲氨基)-2-甲基-3-(2-氯-5-甲氧基 苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.62(brd,J=7.8Hz,2H),7.48(brd,J=7.8Hz,2H), 7.34(brd,J=8.1Hz,1H),7.08(d,J=2.4Hz,1H),6.90-6.88(m,1H),5.19(brs,2H), 3.85(s,3H),3.54(m,2H),3.36-3.14(m,2H),3.14-2.98(m,2H),2.36(s,3H), 2.22(m,2H),1.12-0.98(m,1H),0.64-0.52(m,2H),0.18-0.08(m,2H).
实施例2(247)
8-(N-环丙基甲基-N-(4-三氟甲基苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基 苯基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.65(brd,J=7.5Hz,2H),7.49(brd,J=7.5Hz,2H), 7.33(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H),6.95(dd,J=8.4,2.4Hz,1H),5.35- 5.18(m,6H),3.85(s,3H),3.54(d,J=6.6Hz,2H),2.36(s,3H),1.11(m,1H),0.72- 0.60(m,2H),0.22-0.14(m,2H).
实施例2(248)
8-(N-环丙基甲基-N-(4-三氟甲基苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧 基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.68(d,J=7.8Hz,2H),7.49(d,J=7.8Hz,2H), 7.12(d,J=8.4Hz,1H),6.90(d,J=2.7Hz,1H),6.83(dd,J=8.4,2.7Hz,1H),5.42(m, 2H),5.38(s,2H),5.27(s,2H),3.83(s,3H),3.61(m,2H),2.30(s,3H),2.19(s,3H), 1.15(m,1H),0.74-0.66(m,2H),0.26-0.18(m,2H).
实施例2(249)
8-(N-丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.66(brd,J=7.8Hz,2H),7.49(brd,J=7.8Hz,2H), 7.15(d,J=8.4Hz,1H),6.88(d,J=2.7Hz,1H),6.81(dd,J=8.4,2.7Hz,1H),5.15(brs, 2H),5.09(brs,2H),5.01(brs,2H),3.83(s,3H),3.37(m,2H),2.33(s,3H),2.18(s, 3H),1.74-1.60(m,2H),0.91(t,J=6.9Hz,3H).
实施例2(250)
8-(N-环丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.16-7.07(m,3H),7.02- 6.94(m 2H),6.92(dd,J=8.4,3.0Hz,1H),5.20(s,2H),5.18(s,2H),4.94(s,2H), 3.84(s,3H),2.56(m,1H),2.41(s,3H),0.89-0.79(m,4H).
实施例2(251)
8-(N-环丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.44(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.19-7.08(m,3H),7.04-6.96(m,2H),6.88(d, J=2.7Hz,1H),6.82(dd,J=8.4,2.7Hz,1H),5.28-5.18(m,4H),5.00(s,2H),3.83(s, 3H),2.60(m,1H),2.38(s,3H),2.18(s,3H),0.90-0.80(m,4H).
实施例2(252)
8-(N-环丙基甲基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.36-7.29(m,2H),7.15-7.05(m,3H),6.90(d, J=2.7Hz,1H),6.84(dd,J=8.1,2.7Hz,1H),5.39(s,2H),5.32-5.20(m,4H),3.84(s, 3H),3.62(m,2H),2.32(s,3H),2.20(s,3H),1.20-1.08(m,1H),0.72-0.62(m,2H), 0.28-0.18(m,2H).
实施例2(253)
8-(N-丙基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.35(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.7Hz,1H),7.08(d,J=2.4Hz,1H), 6.97(dd,J=8.7,2.4Hz,1H),5.48(d,J=16.8Hz,1H),5.36(d,J=16.8Hz,1H),5.23(s, 2H),4.38-4.22(m,2H),3.85(s,3H),3.78-3.66(m,4H),3.34(s,3H),2.35(s,3H), 1.81(sext,J=7.5Hz,2H),1.01(t,J=7.5Hz,3H).
实施例2(254)
8-(N-丙基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.33(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.4Hz,1H), 6.83(dd,J=8.4,2.4Hz,1H)5.41(s,2H),5.22(s,2H),4.30(m,2H),3.83(s,3H), 3.80-3.60(m,4H),3.34(s,3H),2.30(s,3H),2.19(s,3H),1.81(sext,J=7.5Hz,2H), 1.01(t,J=7.5Hz,3H).
实施例2(255)
8-(3-戊氨基)-2-甲基-3-(2-甲基-4-氰苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.65(s,1H),7.57(d.J=7.8Hz,1H),7.34(d, J=7.8Hz,1H),7.24-7.08(m,1H),4.06-3.88(m,1H),3.41(brt,J=7.2Hz,2H), 3.15(t,J=7.2Hz,2H),2.40-2.20(m)and 2.30(s)总计8H,1.90-1.40(m,4H),1.06(t, J=6.6Hz,6H).
实施例2(256)
8-(N-丙基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-氯-5-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf 0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34(brd,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.99-6.91(m,1H),4.20(m,2H),3.85(s,3H),3.75(m,2H),3.62(m,2H),3.52- 3.30(m,2H),3.30(s,3H),3.03(m,2H),2.33(s,3H),2.24(m,2H),1.72(m,2H), 0.96(t,J=7.5Hz,3H).
实施例2(257)
8-(N-乙基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.40-7.30(m,1H),7.30-7.16(m,4H),7.08(d, J=2.4Hz,1H),6.99-6.92(m,1H),5.11(brs,2H),3.85(s,3H),3.78(m,2H),3.42(m, 2H),3.00(m,2H),2.50(s,3H),2.35(s,3H),2.21(m,2H),1.34(m,3H).
实施例2(258)
8-(N-乙基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.35(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=8.7Hz,1H),7.28(brd,J=8.1Hz,2H), 7.21(brd,J=8.1Hz,2H),7.09(d,J=2.7Hz,1H),6.97(dd,J=8.7,2.7Hz,1H),5.48- 5.27(m,2H),5.27-5.06(m,4H),3.85(s,3H),3.88-3.78(m,2H),2.50(s,3H), 2.36(s,3H),1.42(t,J=6.9Hz,3H).
实施例2(259)
8-(N-乙基-N-(4-甲基硫苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.28(brd,J=8.4Hz,2H),7.22(brd,J=8.4Hz,2H), 7.13(d,J=8.4Hz,1H),6.90(d,J=2.7Hz,1H),6.84(dd,J=8.4,2.7Hz,1H),5.40(brs, 2H),5.22-5.08(m,4H),3.86(m,2H),3.84(s,3H),2.50(s,3H),2.31(s,3H),2.20(s, 3H),1.43(t,J=6.6Hz,3H).
实施例2(260)
8-(3-戊氨基)-2-甲基-3-(4-甲基硫苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5- a]嘧啶盐酸
TLC:Rf0.46(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.52(d,J=8.4Hz,2H),7.39(d,J=8.4Hz,2H), 7.31(d,J=10.5Hz,1H),4.06-3.90(m,1H),3.60(t,J=7.8Hz,2H),3.13(t,J=7.8Hz, 2H),2.52(s,3H),2.49(s,3H),2.30(quint,J=7.8Hz,2H),1.94-1.64(m,4H),1.05(t, J=7.2Hz,6H).
实施例2(261)
8-(N-丁基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.61(己烷∶乙酸乙酯=1∶2);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.4Hz,1H), 6.82(dd,J=8.4,2.4Hz,1H),5.40(s,2H),5.22(s,2H),4.29(m,2H),3.83(s,3H), 3.78(m,2H),3.72(t,J=5.1Hz,2H),3.34(s,3H),2.30(s,3H),2.19(s,3H), 1.77(quintet,J=7.5Hz,2H),1.42(sixtet,J=7.5Hz,2H),1.00(t,J=7.5Hz,3H).
实施例2(262)
8-(3-戊氨基)-2-甲基-3-(4-二甲氨基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.57(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.72(d,J=7.8Hz,2H),7.60-7.40(m,2H),6.88- 6.75(m,1H),3.98-3.85(m,1H),3.35-3.25(m,2H),3.15-3.05(m)and 3.13(s)total 8H,2.52(s,3H),2.25(quint,J=7.8Hz,2H),1.85-1.60(m,4H),1.03(t,J=7.5Hz, 6H).
实施例2(263)
8-(N-环丙基甲基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.55(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.88(d,J=2.4Hz,1H), 6.81(dd,J=8.4,2.4Hz,1H),5.24(s,2H),5.04(s,2H),3.83(s,3H),3.69-3.63(m, 4H),2.33(s,3H),2.18(s,3H),1.70(sixt,J=7.5Hz,2H),1.07(m,1H),0.96(t, J=7.5Hz,3H),0.56(m,2H),0.20(m,2H).
实施例2(264)
8-(N-丙基-N-(5-甲基呋喃-2-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5, 7 -二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.4Hz,1H),7.08(d,J=2.7Hz,1H), 6.90(dd,J=2.7,8.4Hz,1H),6.02(d,J=3.0Hz,1H),5.86(m,1H),5.08(s,2H), 4.91(s,2H),4.90(s,2H),3.84(s,3H),3.26(m,2H),2.41(s,3H),2.23(s,3H), 1.66(m,2H),0.94(t,J=7.2Hz,3H).
实施例2(265)
8-(N-丙基-N-(5-甲基呋喃-2-基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.18(d,J=8.1Hz,1H),6.88(d,J=2.4Hz,1H), 6.81(d,J=2.4,8.1Hz,1H),6.01(d,J=3.0Hz,1H),5.86(m,1H),5.07(s,2H),4.91(s, 2H),4.88(s,2H),3.83(s,3H),3.25(m,2H),2.37(s,3H),2.22(s,3H),2.18(s,3H), 1.67(m,2H),0.94(t,J=7.5Hz,3H).
实施例2(266)
8-(N-环丙基甲基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.1Hz,1H),6.86(d,J=2.4Hz,1H), 6.80(dd,J=8.1,2.4Hz,1H),5.25(s,2H),4.90(s,2H),4.05(t,J=5.4Hz,2H),3.83(s, 3H),3.56(t,J=5.4Hz,2H),3.48(d,J=6.9H z,2H),3.29(s,3H),2.34(s,3H), 2.17(s,3H),1.04(m,1H),0.56(m,2H),0.22(m,2H).
实施例2(267)
8-(N-丙基-N-(4-三氟甲基氧苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf 0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.36(brd,J=8.1Hz,2H),7.18(brd,J=8.1Hz,2H), 7.17(d,J=8.4Hz,1H),6.88(d,J=2.4Hz,1H),6.81(dd,J=8.4,2.4Hz,1H),5.13(brs, 2H),4.97(brs,2H),4.92(brs,2H),3.83(s,3H),3.34(m,2H),2.36(s,3H),2.18(s, 3H),1.64(m,2H),0.90(t,J=7.2Hz,3H).
实施例2(268)
8-(N-丙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32-7.22(m,2H),7.17(brd,J=8.7Hz,1H), 7.02(m,2H),6.88(d,J=2.4Hz,1H),6.82(brd,J=8.7Hz,1H),5.11(brs,2H), 4.95(brs,4H),3.83(s,3H),3.34(m,2H),2.36(s,3H),2.19(s,3H),1.65(m,2H), 0.90(t,J=6.9Hz,3H).
实施例2(269)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-甲基硫苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.64(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.40-7.34(m,2H),7.33-7.24(m,2H),3.99(m, 1H),3.66-3.35(m,2H),3.13(t,J=7.5Hz,2H),2.52(s,3H),2.35(s,3H),2.30(m, 2H),1.94-1.64(m,4H),1.10-1.00(m,6H).
实施例2(270)
8-(N-环丙基甲基-N-(2-丁炔基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.88(d,J=2.7Hz,1H), 6.81(dd,J=8.1,2.7Hz,1H),5.37(s,2H),5.05(s,2H),4.58(s,2H),3.83(s,3H), 3.62(m,2H),2.35(s,3H),2.17(s,3H),1.84(s,3H),1.20(m,1H),0.63(m,2H), 0.36(m,2H).
实施例2(271)
8-(N-(2-甲氧基乙基)-N-(2-丁炔基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.13(d,J=8.1Hz,1H),6.87(d,J=2.4Hz,1H), 6.81(dd,J=8.1,2.4Hz,1H),5.39(s,2H),5.06(s,2H),4.42(s,2H),4.06(m,2H), 3.83(s,3H),3.81(m,2H),3.37(s,3H),2.33(s,3H),2.17(s,3H),1.85(s,3H).
实施例2(272)
8-(N-(2-甲氧基乙基)-N-(2-丁炔基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)- 5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.39(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.4Hz,1H),7.06(d,J=2.4Hz,1H), 6.89(dd,J=8.4,2.4Hz,1H),5.37(s,2H),4.92(s,2H),4.36(m,2H),3.95(t, J=5.4Hz,2H),3.83(s,3H),3.76(t,J=5.4Hz,2H),3.36(s,3H),2.37(s,3H),1.83(s, 3H).
实施例2(273)
8-(N-(2-甲氧基乙基)-N-(2-丁炔基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)- 6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.44(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.06(d,J=2.7Hz,1H), 6.93(dd,J=8.4,2.7Hz,1H),4.53(m,2H),4.18(m,2H),3.84(s,3H),3.81(t, J=4.8Hz,2H),3.36(s,3H),3.30(m,2H),3.20(t,J=7.2Hz,2H),2.34(s,3H), 2.22(quint,J=7.2Hz,2H),1.86(t,J=2.4Hz,3H).
实施例2(274)
8-(N-丙基-N-(5-甲基呋喃-2-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.06(d,J=2.7Hz,1H), 6.89(dd,J=2.7,8.4Hz,1H),5.99(d,J=3.0Hz,1H),5.85(dd,J=1.6,3.0Hz,1H), 4.78(s,2H),3.84(s,3H),3.35(m,2H),2.90(t,J=7.5Hz,2H),2.81(t,J=7.2Hz,2H), 2.39(s,3H),2.22(m,3H),2.07(m,2H),1.62(m,2H),0.91(t,J=7.5Hz,3H).
实施例2(275)
8-(N-苄基-N-环丙基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.42-7.30(m,4H),7.25-7.15(m,2H),7.09(d, J=2.4Hz,1H),7.00-6.94(m,1H),5.39(d,J=14.7Hz,1H),5.27(d,J=14.7Hz,1H), 3.85(s,3H),3.70-3.32(m,2H),3.12(m,2H),2.96(m,1H),2.37(s,3H),2.21(m, 2H),1.20-0.92(m,4H).
实施例2(276)
8-(N-苄基-N-环丙基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃 并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.30-7.26(m,3H),7.15- 7.09(m,2H),7.08(d,J=2.4Hz,1H),6.91(dd,J=8.4,2.4Hz,1H),5.20(s,2H), 5.19(s,2H),4.91(s,2H),3.84(s,3H),2.56(m,1H),2.41(s,3H),0.92-0.78(m,4H).
实施例2(277)
8-(N-苄基-N-环丙基氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33-7.19(m,3H),7.19(d,J=8.1Hz,1H),7.14- 7.08(m,2H),6.88(d,J=2.7Hz,1H),6.82(dd,J=8.1,2.7Hz,1H),5.32-5.12(m,2H), 5.19(s,2H),4.89(s,2H),3.83(s,3H),2.57(m,1H),2.38(s,3H),2.18(s,3H),0.92- 0.78(m,4H).
实施例2(278)
8-(N-环丙基甲基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.30(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.33(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.94(dd,J=8.4,2.4Hz,1H),5.30(m)and 5.27(s)total 4H,4.32(m,2H),3.84(s,3H), 3.72-3.67(m,4H),3.31(s,3H),2.36(s,3H),1.11(m,1H),0.71(m,2H),0.36(m, 2H).
实施例2(279)
8-(N-环丙基甲基-N-(2-甲氧基乙基)氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.33(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.95(dd,J=8.4,2.4Hz,1H),4.30(m,2H),3.85(s,3H),3.71(d,J=6.6Hz,2H), 3.64(t,J=5.1Hz,2H),3.41(m,2H),3.29(s,3H),3.07(t,J=7.2Hz,2H),2.34(s,3H), 2.24(quint,J=7.2Hz,2H),1.09(m,1H),0.65(m,2H),0.31(m,2H).
实施例2(280)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-bromo苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.65(d,J=2.1Hz,1H),7.44(dd,J=2.1,8.1Hz, 1H),7.28(d,J=8.1Hz,1H),6.23(br d,J=10.5Hz,1H),3.81(m,1H),3.09(t, J=7.2Hz,2H),2.90(t,J=7.8Hz,2H),2.34(s,3H),2.15(m,2H),1.60-1.82(m,4H), 1.01(t,J=7.5Hz,6H).
实施例2(281)
8-(3-戊氨基)-2-甲基-3-(2,5-二氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.65(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.40(s,1H),7.06(s,1H),6.22(br d,J=10.5Hz, 1H),3.92(s,3H),3.81(m,1H),3.08(t,J=6.9Hz,2H),2.91(t,J=7.8Hz,1H),2.33(s, 3H),2.15(m,2H),1.58-1.82(m,4H),1.01(t,J=7.5Hz,6H).
实施例2(282)
8-(3-戊氨基)-2-甲基-3-(2,5-二氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.39(s,1H),7.07(s,1H),6.34(br d,J=10.5Hz, 1H),5.29(m,2H),4.93(m,2H),3.93(s,3H),3.24(m,1H),2.36(s,3H),1.67- 1.84(m,4H),1.02(t,J=7.2Hz,6H).
实施例2(283)
8-(N-环丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-氯4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.61(d,J=7.8Hz,2H),7.33(d,J=7.8Hz,2H), 7.30(d,J=8.7Hz,1H),7.08(d,J=2.7Hz,1H),6.91(dd,J=8.7,2.7Hz,1H),5.27(s, 2H),5.25(s,2H),4.93(s,2H),3.84(s,3H),2.58(m,1H),2.40(s,3H),0.84(m,4H).
实施例2(284)
8-(N-环丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.24(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.61(d,J=7.8Hz,2H),7.33(d,J=7.8Hz,2H), 7.17(d,J=8.1Hz,1H),6.88(d,J=2.7Hz,1H),6.82(dd,J=8.1,2.7Hz,1H),5.40- 5.20(m,2H),5.25(s,2H),4.91(s,2H),3.83(s,3H),2.58(m,1H),2.36(s,3H), 2.17(s,3H),0.84(m,4H).
实施例2(285)
8-二丁氨基-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
TLC:Rf0.66(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=8.4Hz,1H),7.07(d,J=2.1Hz,1H), 6.94(dd,J=8.4,2.1Hz,1H),3.84(s and m,total 7H),3.35(m,2H),3.01(t,J=7.5Hz, 2H),2.33(s,3H),2.22(quint,J=7.5Hz,2H),1.67(quint,J=7.5Hz,4H),1.36(sixt, J=7.5Hz,2H),0.95(t,J=7.5Hz,6H).
实施例2(286)
8-二丁氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.63(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.11(d,J=8.4Hz,1H),6.89(d,J=2.4Hz,1H), 6.83(dd,J=8.4,2.4Hz,1H),5.43(s,2H),5.21(s,2H),3.88(m,4H),3.83(s,3H), 2.29(s,3H),2.20(s,3H),1.78(quint,J=7.5Hz,4H),1.42(sixt,J=7.5Hz,4H), 1.00(t,J=7.5Hz,6H).
实施例2(287)
8-双(2-甲氧基乙基)氨基-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.35(d,J=9.0Hz,1H),7.08(d,J=2.7Hz,1H), 6.96(dd,J=9.0,2.7Hz,1H),4.15(m,4H),3.85(s,3H),3.64(t,J=5.4Hz,4H), 3.53(m,1H),3.45(m,1H),3.31(s,6H),3.05(t,J=7.2Hz,2H),2.34(s,3H), 2.22(quint,J=7.2Hz,2H).
实施例2(288)
8-(N-乙基-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=7.8Hz,1H),7.07(d,J=2.1Hz,1H), 6.92(m,1H),5.28(s,2H),5.11(s,2H),3.84(s,3H),3.81(m,2H),3.69(m,2H), 2.37(s,3H),1.33(s,3H),1.09(m,1H),0.60(m,2H),0.24(m,2H).
实施例2(289)
8-(N-乙基-N-环丙基甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.50(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.12(m,1H),6.89(s,1H),6.82(m,1H),5.38(m, 2H),5.31(m,2H),3.99(m,2H),3.83(s and m,total 5H),2.31(s,3H),2.20(s,3H), 1.44(m,3H),1.19(m,1H),0.72(m,2H),0.36(m,2H).
实施例2(290)
8-(N-乙基-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.4Hz,1H),7.06(d,J=2.4Hz,1H), 6.89(dd,J=8.4,2.4Hz,1H),3.84(s,3H),3.77(q,J=7.2Hz,2H),3.59(d,J=6.6Hz, 2H),3.04(t,J=7.5Hz,4H),2.36(s,3H),2.16(quint,J=7.5Hz,2H),1.23(t,J=7.2Hz, 3H),1.03(m,1H),0.50(m,2H),0.15(m,2H).
实施例2(291)
8-(N-环丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.29(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,DMSO-d6):δ7.83-7.76(m,2H),7.54-7.48(m,2H),7.30(dd, J=8.7,1.2Hz,1H),7.16(m,1H),7.02-6.96(m,1H),5.12(m,2H),3.82(s,3H), 3.06(m,2H),2.94-2.78(m,3H),2.25(s,3H),2.05(m,2H),0.79-0.70(m,2H), 0.61(m,2H).
实施例2(292)
8-(N-环丙基甲基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.37(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.69(brd,J=7.2Hz,2H),7.49(brd,J=7.2Hz,2H), 7.34(brd,J=8.4Hz,1H),7.09(d,J=2.1Hz,1H),6.96(m,1H),5.33(m,2H),3.85(s, 3H),3.60(m,2H),3.48(m,2H),3.10(m,2H),2.33(s,3H),2.28(m,2H),1.18- 1.02(m,1H),0.70-0.58(m,2H),0.22-0.10(m,2H).
实施例2(293)
8-(N-环丙基甲基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.21(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.68(d,J=8.1Hz,2H),7.52(d,J=8.1Hz,2H), 7.31(d,J=8.7Hz,1H),7.08(d,J=2.4Hz,1H),6.94(dd,J=8.7,2.4Hz,1H),5.26(m, 4H),5.14(s,2H),3.84(s,3H),3.45(d,J=6.6H z,2H),2.36(s,3H),1.05(m,1H), 0.68-0.56(m,2H),0.18-0.10(m,2H).
实施例2(294)
8-(N-环丙基甲基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.37(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.66(d,J=7.8Hz,2H),7.52(d,J=7.8Hz,2H), 7.15(d,J=8.1Hz,1H),6.88(d,J=2.4Hz,1H),6.82(dd,J=8.1,2.4Hz,1H),5.25(s, 2H),5.13(s,2H),5.00(s,2H),3.83(s,3H),3.41(d,J=6.6Hz,2H),2.34(s,3H), 2.18(s,3H),1.02(m,1H),0.60-0.52(m,2H),0.12-0.06(m,2H).
实施例2(295)
8-(N-丙基-N-(噻吩-3-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.7Hz,1H),7.28(m,1H),7.13(m,1H), 7.08(d,J=2.4Hz,1H),6.98(dd,J=0.9,4.8Hz,1H),6.90(dd,J=2.4,8.7Hz,1H), 5.08(s,2H),4.96(s,2H),4.89(s,2H),3.84(s,3H),3.32(m,2H),2.41(s,3H), 1.64(m,2H),0.90(t,J=7.5Hz,3H).
实施例2(296)
8-(N-丙基-N-(5-甲基噻吩-2-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.50(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.7Hz,1H),7.07(d,J=2.4Hz,1H), 6.90(dd,J=2.4,8.7Hz,1H),6.66(d,J=3.3Hz,1H),6.56(m,1H),5.02-5.17(m,4H), 4.90(s,2H),3.84(s,3H),3.27(m,2H),2.44(s,3H),2.42(s,3H),1.64(m,2H), 0.92(t,J=7.5Hz,3H).
实施例2(297)
8-(N-丁基-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.7Hz,1H),7.06(d,J=2.1Hz,1H), 6.89(dd,J=8.7,2.1Hz,1H),3.83(s,3H),3.69(t,J=7.2Hz,2H),3.56(d,J=7.2Hz, 2H),3.02(m,4H),2.36(s,3H),2.15(quint,J=7.2Hz,2H),1.58(quint,J=7.5Hz, 2H),1.34(sixt,J=7.5Hz,2H),1.02(m,1H),0.91(t,J=7.5Hz,3H),0.48(m,2H), 0.13(m,2H).
实施例2(298)
8-(N-丁基-N-环丙基甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.40(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.07(d,J=2.1Hz,1H), 6.93(dd,J=8.4,2.1Hz,1H),5.25(s,2H),5.17(s,2H),3.84(s,3H),3.77(m,2H), 3.71(m,2H),2.37(s,3H),1.70(quint,J=7.2Hz,2H),1.39(sixt,J=7.2Hz,2H), 1.10(m,1H),0.96(t,J=7.2Hz,3H),0.62(m,2H),0.25(m,2H).
实施例2(299)
8-(N-丁基-N-环丙基甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.7Hz,1H),6.88(d,J=2.1Hz,1H), 6.81(dd,J=8.7,2.1Hz,1H),5.25(s,2H),5.13(s,2H),3.83(s,3H),3.75(m,2H), 3.70(m,2H),2.33(s,3H),2.18(s,3H),1.69(m,2H),1.39(sixt,J=7.5Hz,2H), 1.09(m,1H),0.96(t,J=7.5Hz,3H),0.60(m,2H),0.23(m,2H).
实施例2(300)
8-(N-丙基-N-(噻吩-3-基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7- 二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.28(dd,J=2.7,5.1Hz,1H),7.18(d,J=8.7Hz, 1H),7.13(m,1H),6.97(dd,J=1.5,5.1Hz,1H),6.88(d,J=3.0Hz,1H),6.81(dd, J=3.0,8.7Hz,1H),5.07(s,2H),4.96(s,2H),4.87(s,2H),3.83(s,3H),3.31(m,2H), 2.37(s,3H),2.19(s,3H),1.64(m,2H),0.91(t,J=7.2Hz,3H).
实施例2(301)
8-(N-丙基-N-(5-甲基噻吩-2-基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.18(d,J=8.4Hz,1H),6.88(d,J=3.0Hz,1H), 6.81(dd,J=3.0,8.4Hz,1H),6.65(d,J=3.3Hz,1H),6.55(m,1H),5.11(s,4H), 4.88(s,2H),3.83(s,3H),3.27(m,2H),2.43(s,3H),2.38(s,3H),2.19(s,3H), 1.65(m,2H),0.92(t,J=7.5Hz,3H).
实施例2(302)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-乙氧基羰基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶盐酸
TLC:Rf0.56(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.21(d,J=1.5Hz,1H),8.08(dd,J=1.5,7.8Hz, 1H),7.56(d,J=7.8Hz,1H),7.30(brd,J=10.8Hz,1H),4.38(q,J=6.9Hz,2H), 4.00(m,1H),3.34-3.64(m,2H),3.15(t,J=6.9Hz,2H),2.35(s,3H),2.31(m,2H), 1.65-1.96(m,4H),1.41(t,J=6.9Hz,3H),1.07(t,J=7.5Hz,3H),1.06(t,J=7.5Hz, 3H).
实施例2(303)
8-(N-丙基-N-(2-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.35(m,2H),7.10-6.92(m,5H),5.16(m,2H), 3.85(s,3H),3.70(m,2H),3.60-3.34(m,2H),3.03(m,2H),2.35(s,3H),2.26(m, 2H),1.75(m,2H),0.94(m,3H).
实施例2(304)
8-(N-丙基-N-(2-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.48-7.33(m,2H),7.13-7.04(m,4H),6.97(dd, J=8.4,2.4Hz,1H),5.50-5.15(m,4H),5.17(s,2H),3.85(s,3H),3.74-3.60(m,2H), 2.37(s,3H),1.82(sext,J=7.2Hz,2H),0.97(t,J=7.2Hz,3H).
实施例2(305)
8-(N-丙基-N-(2-氟苯基)甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.55(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.36-7.26(m,1H),7.16(d,J=8.7Hz,1H),7.09- 6.96(m,3H),6.88(d,J=2.7Hz,1H),6.82(dd,J=8.7,2.7Hz,1H),5.13(s,2H), 5.03(s,2H),5.02(s,2H),3.83(s,3H),3.41(m,2H),2.35(s,3H),2.19(s,3H), 1.69(sext,J=7.2Hz,2H),0.92(t,J=7.2Hz,3H).
实施例2(306)
8-(N-丙基-N-(5-甲基噻吩-2-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.57(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.06(d,J=2.7Hz,1H), 6.89(dd,J=2.7,8.4Hz,1H),6.64(d,J=3.3Hz,1H),6.54(m,1H),4.96(s,2H), 3.84(s,3H),3.38(m,2H),2.90(t,J=7.5Hz,2H),2.86(t,J=7.2Hz,2H),2.43(s,3H), 2.40(s,3H),2.08(m,2H),1.61(m,2H),0.90(t,J=7.5Hz,3H).
实施例2(307)
8-(N-丙基-N-(噻吩-3-基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.53(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.7Hz,1H),7.25(m,1H),7.11(m,1H), 7.07(d,J=2.7Hz,1H),6.95(dd,J=1.5,5.1Hz,1H),6.89(dd,J=2.7,8.7Hz,1H), 4.85(s,2H),3.84(s,3H),3.39(m,2H),2.90(t,J=7.5Hz,2H),2.81(t,J=7.2Hz,2H), 2.39(s,3H),2.07(m,2H),1.60(m,2H),0.89(t,J=7.2Hz,3H).
实施例2(308)
8-(N-乙基-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.58(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30(d,J=8.4Hz,1H),7.06(d,J=2.7Hz,1H), 6.88(dd,J=8.4,2.7Hz,1H),3.83(s,3H),3.66(q,J=6.9Hz,2H),3.60-3.50(m,2H), 3.02-2.84(m,4H),2.37(s,3H),2.20-2.04(m,2H),1.64-1.52(m,2H),1.17(t, J=6.9Hz,3H),0.90(t,J=6.9Hz,3H).
实施例2(309)
8-(N-乙基-N-丙氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.55(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.7Hz,1H),6.87(d,J=2.7Hz,1H), 6.80(dd,J=8.7,2.7Hz,1H),5.20(s,2H),4.89(s,2H),3.82(s,3H),3.67(q,J=7.2Hz, 2H),3.60-3.48(m,2H),2.34(s,3H),2.18(s,3H),1.72-1.56(m,2H),1.23(t, J=7.2Hz,3H),0.93(t,J=7.2Hz,3H).
实施例2(310)
8-(N-乙基-N-丙氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.06(d,J=2.7Hz,1H), 6.89(dd,J=8.7,2.7Hz,1H),5.19(s,2H),4.90(s,2H),3.83(s,3H),3.67(q,J=7.2Hz, 2H),3.60-3.48(m,2H),2.38(s,3H),1.70-1.50(m,2H),1.24(t,J=7.2Hz,3H), 0.93(t,J=7.2Hz,3H).
实施例2(311)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-氨基甲酰基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.53(二氯甲烷∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.96(d,J=1.8Hz,1H),7.70(dd,J=8.1,1.8Hz, 1H),7.50(d,J=8.1Hz,1H),6.26(d,J=10.5Hz,1H),3.82(m,1H),3.14-3.05(m, 2H),2.91(t,J=7.8Hz,2H),2.36(s,3H),2.22-2.10(m,2H),1.85-1.50(m,4H), 1.02(t,J=7.5Hz,6H).
实施例2(312)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-(N-甲基氨基甲酰基)苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.55(二氯甲烷∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.89(d,J=1.8Hz,1H),7.64(dd,J=7.8,1.8Hz, 1H),7.45(d,J=7.8Hz,1H),6.42(brs,1H),6.26(d,J=10.2Hz,1H),3.82(m,1H), 3.14-3.05(m,2H),3.01(d,J=4.5Hz,3H),2.91(t,J=7.8Hz,2H),2.35(s,3H),2.22- 2.09(m,2H),1.82-1.55(m,4H),1.02(t,J=7.5Hz,6H).
实施例2(313)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-(N,N-二甲基氨基甲酰基)苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.65(二氯甲烷∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.56(d,J=1.5Hz,1H),7.46(d,J=7.8Hz,1H), 7.36(dd,J=7.8,1.5Hz,1H),6.26(d,J=9.9Hz,1H),3.82(m,1H),3.17-3.02(m,8H), 2.92(t,J=7.8Hz,2H),2.34(s,3H),2.21-2.06(m,2H),1.85-1.42(m,4H),1.02(t, J=7.5Hz,6H).
实施例2(314)
8-(3-戊氨基)-2-甲基-3-(2,6-二甲基-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.29(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ6.69(s,2H),6.32(d,J=10.8Hz,1H),5.29(s,2H), 4.88(s,2H),3.80(s,3H),3.30-3.18(m,1H),2.22(s,3H),2.04(s,6H),1.83-1.55(m, 4H),1.03(t,J=7.2Hz,6H).
实施例2(315)
8-(N-乙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-甲基4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30-7.22(m,2H),7.18(d,J=8.1Hz,1H),7.06- 6.94(m,2H),6.88(d,J=2.7Hz,1H),6.81(dd,J=8.1,2.7Hz,1H),5.09(s,2H),4.96- 4.80(m,4H),3.83(s,3H),3.41(q,J=7.2Hz,2H),2.37(s,3H),2.18(s,3H),1.23(t, J=7.2Hz,3H).
实施例2(316)
8-(N-乙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.26-7.22(m,2H),7.07(d, J=2.4Hz,1H),7.04-6.94(m,2H),6.90(dd,J=8.4,2.4Hz,1H),4.81(s,2H),3.84(s, 3H),3.47(q,J=7.2Hz,2H),2.90(t,J=7.2Hz,2H),2.82(t,J=7.2Hz,2H),2.40(s, 3H),2.16-1.98(m,2H),1.18(t,J=7.2Hz,3H).
实施例2(317)
8-(N-乙基-N-(4-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.31(d,J=8.1Hz,1H),7.30-7.24(m,2H),7.08(d, J=2.7Hz,1H),7.06-6.94(m,2H),6.91(dd,J=8.1,2.7Hz,1H),5.10(s,2H),4.90(s, 2H),4.89(s,2H),3.84(s,3H),3.42(q,J=7.2Hz,2H),2.40(s,3H),1.22(t,J=7.2Hz, 3H).
实施例2(318)
8-(3-戊氨基)-2-甲基-3-(2-氯-4,6-二甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.26(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ6.67(d,J=2.7Hz,1H),6.45(d,J=2.7Hz,1H), 6.23(d,J=10.8Hz,1H),3.82(s,3H),3.80(m,1H),3.70(s,3H),3.07(m,2H), 2.90(m,2H),2.25(s,3H),2.13(m,2H),1.52-1.80(m,4H),1.02(t,J=7.2Hz,3H), 1.01(t,J=7.2Hz,3H).
实施例2(319)
8-(3-戊氨基)-2-甲基-3-(2-氯-4,6-二甲氧基苯基)-5,7-二氢-呋喃并[3,4-d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.22(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ6.68(d,J=2.7Hz,1H),6.47(d,J=2.7Hz,1H), 6.34(d,J=10.8Hz,1H),5.28(s,2H),4.92(d,J=13.5Hz,1H),4.90(d,J=13.5Hz, 1H),3.83(s,3H),3.71(s,3H),3.23(m,1H),2.28(s,3H),1.53-1.82(m,4H),1.02(t, J=7.5Hz,3H),1.01(t,J=7.5Hz,3H).
实施例2(320)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-氨基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.22(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.82(d,J=2.1Hz,1H), 6.63(dd,J=8.4,2.1Hz,1H),6.21(d,J=10.2Hz,1H),3.87-3.62(m,3H),3.12- 3.03(m,2H),2.95-2.86(m,2H),2.34(s,3H),2.20-2.07(m,2H),1.85-1.50(m,4H), 1.01(t,J=7.5Hz,6H).
实施例2(321)
8-(4-庚氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.7Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.7,2.7Hz,1H),6.32(d,J=10.8Hz,1H),5.29(s,2H),4.90(s,2H), 3.82(s,3H),3.40(m,1H),2.32(s,3H),2.18(s,3H),1.78-1.38(m,8H),0.95(t, J=7.2Hz,6H).
实施例2(322)
8-(3-戊氨基)-2-甲基-3-(2-氯-4-甲氨基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.45(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.18(d,J=8.4Hz,1H),6.73(d,J=2.4Hz,1H), 6.56(dd,J=8.4,2.4Hz,1H),6.21(d,J=10.5Hz,1H),3.88-3.70(m,2H),3.12- 3.02(m,2H),2.95-2.80(m,2H),2.85(s,3H),2.34(s,3H),2.20-2.05(m,2H),1.80- 1.50(m,4H),1.01(t,J=7.2Hz,6H).
实施例2(323)
8-(3-戊氨基)-2-甲基-3-(2-甲酰基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.26(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ9.85(s,1H),7.55(d,J=2.7Hz,1H),7.38(d, J=8.4Hz,1H),7.22(dd,J=8.4,2.7Hz,1H),6.23(d,J=9.6Hz,1H),3.93- 3.74(m)and 3.89(s)total 4H,3.09(t,J=7.5Hz,2H),2.88(t,J=7.5Hz,2H),2.39(s, 3H),2.14(quint,J=7.5Hz,2H),1.83-1.50(m,4H),1.02(t,J=7.5Hz,6H).
实施例2(324)
8-(3-戊氨基)-2-甲基-3-(2-氰基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.54(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.46(d,J=9.0Hz,1H),7.24(d,J=2.4Hz,1H), 7.18(dd,J=9.0,2.4Hz,1H),6.24(d,J=10.5Hz,1H),3.88-3.73(m)and 3.86(s)total 4H,3.09(t,J=7.2Hz,2H),2.92(t,J=7.2Hz,2H),2.43(s,3H),2.15(quint,J=7.2Hz, 2H),1.80-1.50(m,4H),1.02(t,J=7.2Hz,6H).
实施例2(325)
8-(3-戊氨基)-2-甲基-3-(2-乙基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.30(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.12(d,J=8.4Hz,1H),6.88(d,J=2.4Hz,1H), 6.77(dd,J=8.4,2.4Hz,1H),6.21(d,J=10.5Hz,1H),3.83-3.75(m)and 3.83(s)total 4H,3.08(t,J=7.2Hz,2H),2.88(t,J=7.2Hz,2H),2.52(q,J=7.8Hz,2H),2.28(s, 3H),2.13(quint,J=7.2Hz,2H),1.83-1.50(m,4H),1.10-0.98(m,9H).
实施例2(326)
8-(4-庚氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶盐酸
TLC:Rf0.51(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.20(s,1H),7.65(d,J=8.4Hz,1H),7.38(d, J=10.2Hz,1H),7.08-6.97(m,2H),4.15(m,1H),3.84(s,3H),3.61(m,2H),3.16(m, 2H),2.33(m,2H),1.88-1.60(m,4H),1.60-1.35(m,4H),0.99(t,J=7.5Hz,6H).
实施例2(327)
8-(N,N-二丙氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.54(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.32(s,1H),7.78(d,J=8.7Hz,1H),7.03(d, J=2.7Hz,1H),6.91(dd,J=8.7,2.7Hz,1H),3.83(s,3H),3.57(m,4H),2.97(m,4H), 2.17(m,2H),1.66-1.50(m,4H),0.88(t,J=7.5Hz,6H).
实施例2(328)
8-(N,N-二丙氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.58(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.35(s,1H),7.72(d,J=9.0Hz,1H),7.04(d, J=2.4Hz,1H),6.91(dd,J=9.0,2.4Hz,1H),5.20(s,2H),4.94(s,2H),3.82(s,3H), 3.57(t,J=7.5Hz,4H),1.72-1.46(m,4H),0.90(t,J=7.2Hz,6H).
实施例2(329)
8-(N-环丙基甲基-N-丙氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.60(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.73(d,J=8.4Hz,1H),7.05(d, J=2.7Hz,1H),6.92(dd,J=8.4,2.7Hz,1H),5.25(s,2H),4.96(s,2H),3.83(s,3H), 3.64-3.50(m,4H),1.72-1.56(m,2H),1.04(m,1H),0.93(t,J=7.5Hz,3H),0.58- 0.44(m,2H),0.20-0.08(m,2H).
实施例2(330)
8-(N-苄基-N-环丙基甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.42(s,1H),7.74(d,J=8.4Hz,1H),7.38-7.20(m, 5H),7.06(d,J=2.7Hz,1H),6.93(dd,J=8.4,2.7Hz,1H),5.25(s,2H),4.96(s,2H), 4.95(s,2H),3.84(s,3H),3.43(d,J=6.6Hz,2H),1.04(m,1H),0.58-0.46(m,2H), 0.16-0.04(m,2H).
实施例2(331)
8-(N-环丙基甲基-N-(4-甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二 氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.56(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.42(s,1H),7.75(d,J=8.4Hz,1H),7.19(d, J=7.8Hz,2H),7.13(d,J=7.8Hz,2H),7.06(d,J=2.4Hz,1H),6.93(dd,J=8.4,2.4Hz, 1H),5.24(s,2H),4.95(s,2H),4.91(s,2H),3.84(s,3H),3.42(d,J=6.3Hz,2H), 2.33(s,3H),1.04(m,1H),0.58-0.46(m,2H),0.18-0.04(m,2H).
实施例2(332)
8-(N-丙基-N-(2-丁炔基)氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.41(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.71(d,J=8.7Hz,1H),7.05(d, J=2.7Hz,1H),6.92(dd,J=8.7,2.7Hz,1H),5.34(s,2H),4.97(s,2H),4.44(q, J=2.4Hz,2H),3.83(s,3H),3.52(m,2H),1.82(t,J=2.4Hz,3H),1.80-1.62(m,2H), 0.98(t,J=7.2Hz,3H).
实施例2(333)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基羰基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.26(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.70(d,J=2.7Hz,1H),7.34(d,J=8.4Hz,1H), 7.30-7.16(m)and 7.19(dd,J=8.4,2.7Hz)total 2H,4.03-3.83(m)and 3.89(s)total 4H, 3.77(s,3H),3.54-3.36(m,2H),3.11(t,J=7.5Hz,2H),2.33-2.00(m)and 2.25(s)total 4H,1.90-1.58(m,4H),1.05(t,J=7.5Hz,6H).
实施例2(334)
8-(N-丁基-N-环丙基甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.74(d,J=9.0Hz,1H),7.05(d, J=2.7Hz,1H),6.91(dd,J=9.0,2.7Hz,1H),5.25(s,2H),4.96(s,2H),3.83(s,3H), 3.66-3.52(m,4H),1.66-1.48(m,2H),1.44-1.22(m,2H),1.04(m,1H),0.91(t, J=7.2Hz,3H),0.60-0.44(m,2H),0.22-0.08(m,2H).
实施例2(335)
8-(3-戊氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑[1,5-a] 嘧啶
TLC:Rf0.57(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.32(s,1H),7.74(d,J=8.7Hz,1H),7.04(d, J=2.7Hz,1H),6.91(dd,J=8.7,2.7Hz,1H),6.42(d,J=10.8Hz,1H),5.31(s,2H), 4.97(s,2H),3.83(s,3H),3.28(m,1H),1.84-1.54(m,4H),1.01(t,J=7.2Hz,6H).
实施例2(336)
8-(N-环丙基甲基-N-(4-氟苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.41(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.41(s,1H),7.74(d,J=9.0Hz,1H),7.38-7.24(m, 2H),7.12-6.96(m,3H),6.92(dd,J=9.0,2.7Hz,1H),5.25(s,2H),4.95(s,2H), 4.91(s,2H),3.84(s,3H),3.39(d,J=6.9Hz,2H),1.02(m,1H),0.60-0.44(m,2H), 0.16-0.02(m,2H).
实施例2(337)
8-(N-环丙基-N-(2-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.41(甲苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.4Hz,1H),7.23(m,1H),7.13-6.97(m, 3H),7.06(d,J=2.7Hz,1H),6.89(dd,J=8.4,2.7Hz,1H),5.15(brs,2H),3.84(s,3H), 2.98-2.86(m,4H),2.83(m,1H),2.40(s,3H),2.02(m,2H),0.84-0.72(m,4H).
实施例2(338)
8-(N-环丙基甲基-N-(2-氟苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.49(甲苯∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.7Hz,1H),7.35-7.16(m,2H),7.06(d, J=2.4Hz,1H),7.08-6.97(m,2H),6.89(dd,J=8.7Hz,2.4Hz,1H),5.02(s,2H), 3.84(s,3H),3.41(d,J=6.9Hz,2H),2.98-2.84(m,4H),2.40(s,3H),2.07(m,2H), 1.05(m,1H),0.48(m,2H),0.10(m,2H).
实施例2(339)
8-(N-环丙基甲基-N-丙氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.76(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.32(s,1H),7.78(d,J=8.7Hz,1H),7.03(d, J=2.7Hz,1H),6.91(dd,J=8.7,2.7Hz,1H),3.83(s,3H),3.68-3.58(m,2H),3.52(d, J=6.9Hz,2H),3.06-2.90(m,4H),2.26-2.08(m,2H),1.66-1.46(m,2H),1.01(m, 1H),0.90(t,J=7.2Hz,3H),0.52-0.42(m,2H),0.16-0.04(m,2H).
实施例2(340)
8-(N-丙基-N-(4-甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.79(d,J=9.0Hz,1H),7.18-7.07(m, 4H),7.04(d,J=2.7Hz,1H),6.92(dd,J=9.0,2.7Hz,1H),4.79(s,2H),3.83(s,3H), 3.45-3.36(m,2H),2.96(t,J=7.8Hz,2H),2.89(t,J=7.8Hz,2H),2.32(s,3H),2.20- 2.04(m,2H),1.66-1.46(m,2H),0.87(t,J=7.2Hz,3H).
实施例2(341)
8-(N-苄基-N-环丙基甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.67(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.38(s,1H),7.79(d,J=8.7Hz,1H),7.38-7.18(m, 5H),7.05(d,J=2.4Hz,1H),6.92(dd,J=8.7,2.4Hz,1H),4.92(s,2H),3.83(s,3H), 3.40(d,J=6.9Hz,2H),3.01(t,J=7.2Hz,2H),2.97(t,J=7.8Hz,2H),2.22-2.06(m, 2H),1.02(m,1H),0.54-0.42(m,2H),0.12-0.02(m,2H).
实施例2(342)
8-(N-环丙基甲基-N-(4-甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.71(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.79(d,J=8.4Hz,1H),7.20(d, J=8.1Hz,2H),7.11(d,J=8.1Hz,2H),7.05(d,J=2.7Hz,1H),6.92(dd,J=8.4,2.7Hz, 1H),4.88(s,2H),3.83(s,3H),3.39(d,J=6.6Hz,2H),3.01(t,J=7.2Hz,2H),2.97(t, J=7.8Hz,2H),2.32(s,3H),2.22-2.06(m,2H),1.02(m,1H),0.54-0.42(m,2H), 0.14-0.02(m,2H).
实施例2(343)
8-(N-丙基-N-(4-氟苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.79(d,J=8.7Hz,1H),7.30-7.22(m, 2H),7.05(d,J=2.4Hz,1H),7.04-6.96(m,2H),6.92(dd,J=8.7,2.4Hz,1H),4.78(s, 2H),3.83(s,3H),3.46-3.34(m,2H),2.97(t,J=7.8Hz,2H),2.89(t,J=7.2Hz,2H), 2.20-2.04(m,2H),1.66-1.48(m,2H),0.87(t,J=7.5Hz,3H).
实施例2(344)
8-二环丙基甲基氨基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.58(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.28(s,1H),7.78(d,J=8.7Hz,1H),7.03(d, J=2.4Hz,1H),6.91(dd,J=8.7,2.4Hz,1H),6.42(d,J=9.6Hz,1H),3.82(s,3H), 3.44(m,1H),3.10-3.00(m,2H),2.98-2.88(m,2H),2.22-2.06(m,2H),1.20- 1.06(m,2H),0.68-0.48(m,4H),0.48-0.34(m,4H).
实施例2(345)
8-(4-庚氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5- a]嘧啶
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.32(s,1H),7.74(d,J=8.7Hz,1H),7.04(d, J=2.7Hz,1H),6.92(dd,J=8.7,2.7Hz,1H),6.42(d,J=10.8Hz,1H),5.32(s,2H), 4.97(s,2H),3.83(s,3H),3.42(m,1H),1.78-1.26(m,8H),0.95(t,J=7.2Hz,6H).
实施例2(346)
8-(N-丙基-N-(4-甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.41(s,1H),7.75(d,J=8.7Hz,1H),7.16-7.08(m, 4H),7.06(d,J=2.4Hz,1H),6.92(dd,J=8.7,2.4Hz,1H),5.14(s,2H),4.95(s,2H), 4.88(s,2H),3.84(s,3H),3.42-3.28(m,2H),2.33(s,3H),1.72-1.50(m,2H),0.89(t, J=7.5Hz,3H).
实施例2(347)
8-(N-丙基-N-(4-氟苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃 并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.50(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.41(s,1H),7.74(d,J=8.4Hz,1H),7.32-7.18(m, 2H),7.08-6.97(m,3H),6.93(dd,J=8.4,2.4Hz,1H),5.15(s,2H),4.95(s,2H), 4.88(s,2H),3.84(s,3H),3.40-3.26(m,2H),1.70-1.48(m,2H),0.89(t,J=7.2Hz, 3H).
实施例2(348)
8-二环丙基甲基氨基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.47(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.33(s,1H),7.73(d,J=8.7Hz,1H),7.04(d, J=2.7Hz,1H),6.91(dd,J=8.7,2.7Hz,1H),6.55(d,J=9.6Hz,1H),5.25(s,2H), 4.94(s,2H),3.83(s,3H),2.92(m,1H),1.22-1.06(m,2H),0.70-0.48(m,4H),0.48- 0.30(m,4H).
实施例2(349)
8-(N-环丙基甲基-N-(4-三氟甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.42(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.41(s,1H),7.73(d,J=8.4Hz,1H),7.60(d, J=8.1Hz,2H),7.50(d,J=8.1Hz,2H),7.06(d,J=2.7Hz,1H),6.93(dd,J=8.4,2.7Hz, 1H),5.27(s,2H),5.02(s,2H),4.96(s,2H),3.84(s,3H),3.40(d,J=6.6Hz,2H), 1.02(m,1H),0.60-0.46(m,2H),0.16-0.04(m,2H).
实施例2(350)
8-(N-环丙基-N-(4-甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.60(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.36(s,1H),7.80(d,J=8.4Hz,1H),7.12-6.99(m, 5H),6.93(dd,J=8.4,2.7Hz,1H),4.96(s,2H),3.83(s,3H),2.97(t,J=7.8Hz,2H), 2.94(t,J=7.5Hz,2H),2.78(m,1H),2.32(s,3H),2.16-2.00(m,2H),0.82-0.68(m, 4H).
实施例2(351)
8-(N-环丙基甲基-N-(4-三氟甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.55(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.78(d,J=8.7Hz,1H),7.58(d, J=8.1Hz,2H),7.49(d,J=8.1Hz,2H),7.05(d,J=2.7Hz,1H),6.92(dd,J=8.7,2.7Hz, 1H),4.97(s,2H),3.83(s,3H),3.39(d,J=6.6Hz,2H),3.04(t,J=7.2Hz,2H),2.99(t, J=7.8Hz,2H),2.18(m,2H),1.01(m,1H),0.56-0.42(m,2H),0.14-0.02(m,2H).
实施例2(352)
8-(3-戊氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a] 嘧啶
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.27(s,1H),7.79(d,J=8.7Hz,1H),7.03(d, J=2.4Hz,1H),6.91(dd,J=8.7,2.4Hz,1H),6.30(d,J=10.2Hz,1H),3.82(s,3H), 3.82(m,1H),3.11(t,J=7.2Hz,2H),2.96(t,J=7.8Hz,2H),2.24-2.08(m,2H),1.84- 1.52(m,4H),1.01(t,J=7.5Hz,6H).
实施例2(353)
8-(N-环丙基甲基-N-(4-氟苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.37(s,1H),7.78(d,J=8.7Hz,1H),7.38-7.24(m, 2H),7.05(d,J=2.7Hz,1H),7.05-6.93(m,2H),6.92(dd,J=8.7,2.7Hz,1H),4.87(s, 2H),3.83(s,3H),3.37(d,J=6.9Hz,2H),3.01(t,J=7.5Hz,2H),2.97(t,J=7.5Hz, 2H),2.22-2.06(m,2H),1.00(m,1H),0.54-0.40(m,2H),0.12-0.02(m,2H).
实施例2(354)
8-(3-戊氨基)-2-甲基-3-(2-(1-甲基-1-羟乙基)-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.50(己烷∶乙酸乙酯=1∶2);
NMR(300MHz,CDCl3):δ7.23(d,J=2.7Hz,1H),7.03(d,J=8.7Hz,1H), 6.83(dd,J=8.7,2.7Hz,1H),6.26(d,J=10.2Hz,1H),5.00-4.85(m,1H),3.85- 3.75(m)and 3.84(s)total 4H,3.06(t,J=6.9Hz,2H),2.85(t,J=6.9Hz,2H),2.29(s, 3H),2.11(quint,J=7.5Hz,2H),1.80-1.50(m)and 1.64(s)total 7H,1.30(s,3H), 1.03(t,J=7.2Hz)and 1.00(t,J=7.2Hz)total 6H。
实施例2(355)
8-(N-丙基-N-(4-三氟甲基氧苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.52(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=9.0Hz,2H),7.32(d,J=8.4Hz,1H), 7.15(d,J=9.0Hz,2H),7.07(d,J=2.7Hz,1H),6.89(dd,J=8.4,2.7Hz,1H),4.84(s, 2H),3.84(s,3H),3.44-3.32(m,2H),2.91(t,J=7.5Hz,2H),2.84(t,J=7.8Hz,2H), 2.39(s,3H),2.06-1.98(m,2H),1.66-1.48(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(356)
8-(3-己基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.44(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30(d,J=8.7Hz,1H),7.05(d,J=2.4Hz,1H), 6.88(dd,J=8.7,2.4Hz,1H),6.22(d,J=10.8Hz,1H),3.84(m,1H),3.83(s,3H), 3.08(t,J=7.5Hz,2H),2.90(t,J=7.8Hz,2H),2.34(s,3H),2.20-2.04(m,2H),1.80- 1.32(m,6H),1.00(t,J=6.9Hz,3H),0.95(t,J=6.9Hz,3H).
实施例2(357)
8-(3-戊氨基)-2-甲基-3-(2-甲氧基-4-甲基吡啶-5-基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.23(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.00(s,1H),6.69(s,1H),6.23(d,J=10.5Hz,1H), 3.94(s,3H),3.82(m,1H),3.08(t,J=7.5Hz,2H),2.89(t,J=7.8Hz,2H),2.32(s,3H), 2.20-2.06(m,2H),2.18(s,3H),1.82-1.54(m,4H),1.02(t,J=7.2Hz,6H).
实施例2(358)
8-(N-丁基-N-环丙基甲氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.27(s,1H),7.71(d,J=8.4Hz,1H),7.04(d, J=2.4Hz,1H),6.94(m,1H),3.90-3.70(m,2H),3.83(s,3H),3.64(d,J=6.6Hz,2H), 3.30-3.12(m,2H),3.12-2.96(m,2H),2.32-2.12(m,2H),1.68-1.50(m,2H),1.46- 1.20(m,2H),1.06(m,1H),0.91(t,J=7.2Hz,3H),0.62-0.46(m,2H),0.24-0.10(m, 2H).
实施例2(359)
8-(N-环丙基-N-(4-甲基苯基)甲氨基)-3-(2-氯-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ8.42(s,1H),7.76(d,J=8.7Hz,1H),7.09(d, J=8.1Hz,2H),7.06(d,J=2.7Hz,1H),6.99(d,J=8.1Hz,2H),6.93(dd,J=8.7,2.7Hz, 1H),5.19(s,2H),5.11(s,2H),4.96(s,2H),3.84(s,3H),2.58(m,1H),2.32(s,3H), 0.86-0.76(m,4H).
实施例2(360)
8-(N-丙基-N-(4-甲基苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.74(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.32(d,J=8.7Hz,1H),7.16-7.06(m,4H),7.07(d, J=3.0Hz,1H),6.89(dd,J=8.7,3.0Hz,1H),4.80(s,2H),3.84(s,3H),3.42-3.30(m, 2H),2.89(t,J=7.8Hz,2H),2.82(t,J=7.2Hz,2H),2.39(s,3H),2.33(s,3H),2.04- 1.98(m,2H),1.70-1.48(m,2H),0.87(t,J=7.2Hz,3H).
实施例2(361)
8-(N-丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢 -呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.38(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.64(d,J=8.1Hz,2H),7.50(d,J=8.1Hz,2H), 7.30(d,J=8.4Hz,1H),7.08(d,J=2.7Hz,1H),6.90(d,J=8.4,2.7Hz,1H),5.14(s, 2H),5.01(s,2H),4.91(s,2H),3.84(s,3H),3.36-3.22(m,2H),2.38(s,3H),1.70- 1.50(m,2H),0.89(t,J=7.2Hz,3H).
实施例2(362)
8-(N-丙基-N-(4-氰苯基)甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.61(d,J=7.8Hz,2H),7.47(d,J=7.8Hz,2H), 7.31(d,J=8.4Hz,1H),7.07(d,J=2.7Hz,1H),6.89(dd,J=8.4,2.7Hz,1H),4.90(s, 2H),3.84(s,3H),3.44-3.32(m,2H),2.92(t,J=7.8Hz,2H),2.88(t,J=7.5Hz,2H), 2.38(s,3H),2.20-2.02(m,2H),1.66-1.46(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(363)
8-(N-环丙基甲基-N-甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.30(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.30(d,J=8.4Hz,1H),7.05(d,J=3.0Hz, 1H),6.88(dd,J=8.4,3.0Hz,1H),3.83(s,3H),3.61(d,J=6.9Hz,2H),3.30(s, 3H),3.12(t,J=7.2Hz,2H),2.92(t,J=7.5Hz,2H),2.36(s,3H),2.20-2.06(m, 2H),1.09(m,1H),0.60-0.46(m,2H),0.24-0.12(m,2H).
实施例2(364)
8-(N-环丙基甲基-N-甲氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-5,7-二氢- 呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.22(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.87(d,J=3.0Hz, 1H),6.80(dd,J=8.4,3.0Hz,1H),5.35(s,2H),4.89(s,2H),3.83(s,3H),3.72(dd, J=6.9,1.5Hz,2H),3.27(s,3H),2.34(s,3H),2.15(s,3H),1.10(m,1H),0.60-0.48(m, 2H),0.24-0.14(m,2H).
实施例2(365)
8-(N-环丙基甲基-N-甲氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋 喃并[3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.18(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.06(d,J=2.7Hz, 1H),6.88(dd,J=8.7,2.7Hz,1H),5.35(s,2H),4.91(s,2H),3.83(s,3H),3.71(d, J=6.9Hz,2H),3.27(s,3H),2.38(s,3H),1.10(m,1H),0.62-0.50(m,2H),0.26- 0.16(m,2H).
实施例2(366)
8-(4-庚氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.55(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.80(s,1H),6.83(s,2H),6.27(d,J=11.1Hz,1H), 3.98(m,1H),3.80(s,3H),3.11(t,J=7.5Hz,2H),2.91(t,J=7.8Hz,2H),2.22- 2.04(m,2H),2.13(s,6H),1.76-1.30(m,8H),0.96(t,J=7.2Hz,6H).
实施例2(367)
8-二丙氨基-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.54(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.86(s,1H),6.69(s,2H),3.80(s,3H),3.64- 3.46(m,4H),2.98(t,J=7.2Hz,2H),2.92(t,J=7.5Hz,2H),2.22-2.00(m,2H), 2.12(s,6H),1.68-1.48(m,4H),0.89(t,J=7.5Hz,6H).
实施例2(368)
8-(N-环丙基甲基-N-丙氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.86(s,1H),6.69(s,2H),3.80(s,3H),3.68- 3.58(m,2H),3.54(d,J=6.6Hz,2H),3.03(t,J=7.5Hz,2H),2.93(t,J=7.5Hz,2H), 2.04-2.00(m,2H),2.12(s,6H),1.68-1.50(m,2H),1.02(m,1H),0.91(t,J=7.5Hz, 3H),0.54-0.40(m,2H),0.18-0.04(m,2H).
实施例2(369)
8-(N-苄基-N-环丙基甲氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.49(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.93(s,1H),7.42-7.08(m,5H),6.70(s,2H), 4.94(s,2H),3.81(s,3H),3.41(d,J=6.6Hz,2H),3.02(t,J=7.5Hz,2H),2.92(t, J=7.8Hz,2H),2.22-2.04(m,2H),2.13(s,6H),1.03(m,1H),0.54-0.38(m,2H), 0.12-0.01(m,2H).
实施例2(370)
8-(N-环丙基甲基-N-(4-甲基苯基甲基)氨基)-3-(2,6-二甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.53(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.92(s,1H),7.21(d,J=8.1Hz,2H),7.11(d, J=8.1Hz,2H),6.70(s,2H),4.89(s,2H),3.81(s,3H),3.40(d,J=6.9Hz,2H),3.02(t, J=7.2Hz,2H),2.92(t,J=7.5Hz,2H),2.32(s,3H),2.22-2.04(m,2H),2.13(s,6H), 1.03(m,1H),0.54-0.40(m,2H),0.10-0.01(m,2H).
实施例2(371)
8-(N-丙基-N-(4-氟苯基甲基)氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.46(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.92(s,1H),7.36-7.18(m,2H),7.06-6.88(m, 2H),6.70(s,2H),4.80(s,2H),3.81(s,3H),3.46-3.32(m,2H),3.00-2.80(m,4H), 2.22-2.00(m,2H),2.13(s,6H),1.70-1.48(m,2H),0.88(t,J=7.2Hz,3H).
实施例2(372)
8-二环丙基甲基氨基-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.45(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.81(s,1H),6.68(s,2H),6.40(d,J=9.9Hz,1H), 3.80(s,3H),3.46(m,1H),3.05(t,J=7.5Hz,2H),2.89(t,J=7.8Hz,2H),2.22- 2.02(m,2H),2.13(s,6H),1.20-1.06(m,2H),0.68-0.36(m,8H).
实施例2(373)
8-(N-丁基-N-环丙基甲氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.61(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.87(s,1H),6.69(s,2H),3.80(s,3H),3.76- 3.60(m,2H),3.53(d,J=6.9Hz,2H),3.03(t,J=7.2Hz,2H),2.93(t,J=7.5Hz,2H), 2.22-2.00(m,2H),2.12(s,6H),1.64-1.46(m,2H),1.42-1.22(m,2H),1.02(m,1H), 0.90(t,J=7.2Hz,3H),0.56-0.38(m,2H),0.18-0.02(m,2H).
实施例2(374)
8-(N-环丙基甲基-N-(4-氟苯基)甲氨基)-3-(2,6-二甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.51(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.92(s,1H),7.38-7.26(m,2H),7.06-6.94(m, 2H),6.71(s,2H),4.89(s,2H),3.81(s,3H),3.39(d,J=6.6Hz,2H),3.02(t,J=7.2Hz, 2H),2.93(t,J=7.2Hz,2H),2.22-2.00(m,2H),2.13(s,6H),1.01(m,1H),0.54- 0.40(m,2H),0.10-0.01(m,2H).
实施例3
8-(N-乙基-N-正-丁氨基)-2-羟基甲基-3-(2-甲基-4-羟基苯基)-6,7-二氢- 5H-环戊[d]吡唑并[1,5-a]嘧啶
向实施例实施例2(1)中制备的化合物(506mg)在二氯甲烷(14ml)中的冷 却至-78℃的溶液中,加入在二氯甲烷(12ml)中的1M三溴化硼。将该反应混 合物倒入碳酸氢钠的饱和水溶液中,并将所得溶液用乙酸乙酯萃取。将所得 溶液用饱和氯化钠水溶液洗涤,在无水硫酸钠上干燥。将残余物在硅胶柱 色谱(正己烷∶乙酸乙酯=1∶1→2∶3)上纯化,得到标题化合物(303mg),其具 有如下物理数据:
TLC:Rf0.14(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ9.41(brs,1H),6.90(d,J=9.0Hz,1H),6.42(m,2 H),4.71(brs,2H),3.70(q,J=7.5Hz,2H),3.64(t,J=7.5Hz,2H),3.01(t,J=7.8Hz, 4H),2.39(brs,1H),2.18(m,2H),2.01(s,3H),1.58(m,2H),1.35(m,2H), 1.21(t,J=7.5Hz,3H),0.91(t,J=7.5Hz,3H).
实施例4
8-(N-乙基-N-正-丁氨基)-2-羟基甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢 -5H-环戊[d]吡唑并[1,5-a]嘧啶
向实施例实施例3中制备的化合物(985mg)在二氯甲烷(10ml)中的冷 却至0℃的溶液中,加入氢化钠(95mg;在油中的63.1%分散体)。将该混合 物搅拌30分钟。将甲基碘(0.18ml)加入反应混合物中,并将所得混合物在 0℃下搅拌2小时。将饱和氯化铵水溶液加入反应混合物中,并将所得溶液 用乙酸乙酯萃取。将有机层相继用1M氢氧化钠水溶液和氯化钠饱和溶液 洗涤,在无水硫酸钠上干燥。将残余物在硅胶柱色谱(甲苯∶乙酸乙酯=5∶1→ 4∶1→7∶2)上纯化,得到标题化合物(947mg),它具有如下物理数据:
TLC:Rf0.35(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.19(d,J=8.4Hz,1H),6.85(d,J=2.7Hz,1H), 6.78(dd,J=8.4,2.7Hz,1H),4.73(d,J=5.7Hz,2H),3.82(s,3H),3.65(q,J=7.2Hz, 2H),3.59(t,J=7.2Hz,2H),2.98(t,J=6.9Hz,2H),2.92(t,J=7.8Hz,2H),2.35(m, 1H),2.19(s,3H),2.15(m,2H),1.55(m,2H),1.35(m,2H),1.18(t,J=7.2Hz,3 H),0.90(t,J=7.2Hz,3H).
实施例5
8-(N-丙基-N-(2-甲氧基亚氨基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-6,7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
向实施例2(2)中制备的化合物(186mg)在二甲亚砜(5ml)中的溶液中, 加入三乙胺(0.39ml)和三氧化硫吡啶复合物(225mg)。将该混合物在室温下 搅拌2小时。将该反应混合物倒入水中并用乙酸乙酯萃取。将所得溶液用 饱和氯化钠水溶液洗涤,在无水硫酸钠上干燥。向该残余物在吡啶(5ml)中 的溶液中,加入邻甲基羟胺盐酸(28mg)。将该混合物在室温下搅拌15小时。 将该反应混合物浓缩并用乙酸乙酯稀释。将该稀释的溶液相继用饱和碳酸 氢钠水溶液和氯化钠饱和溶液洗涤,在无水硫酸钠上干燥。将残余物在硅 胶柱色谱(正己烷∶乙酸乙酯=4∶1→3∶1)上纯化,得到标题化合物(16mg),它 具有如下物理数据:
TLC:Rf0.78(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):
主要异构体
δ7.57(t,J=5.7Hz,1H),7.15(d,J=8.4Hz,1H),6.86(d,J=2.4Hz,1H), 6.79(dd,J=8.4,2.4Hz,1H),4.35(d,J=6.0Hz,2H),3.86(s,3H),3.82(s,3H),3.49(t, J=7.8Hz,2H),2.99(t,J=7.2Hz,2H),2.91(t,J=7.5Hz,2H),2.32(s,3H),2.18(s, 3H),2.14(m,2H),1.58(m,2H),0.90(t,J=7.2Hz,3H)
次要异构体
δ7.15(d,J=8.4Hz,1H),6.95(t,J=3.9Hz,1H),6.86(d,J=2.4Hz,1H), 6.79(dd,J=8.4,2.4Hz,1H),4.47(d,J=4.2Hz,2H),3.90(s,3H),3.82(s,3H),3.54(t, J=7.8Hz,2H),2.99(t,J=7.2Hz,2H),2.91(t,J=7.5Hz,2H),2.32(s,3H),2.18(s, 3H),2.14(m,2H),1.58(m,2H),0.92(t,J=7.2Hz,3H).
实施例5(1)-5(2)
按与实施例5的反应相同的工艺,用实施例2(26)中制备的化合物或实 施例4中制备的化合物和羟基胺盐酸代替邻-甲基羟基胺盐酸,制备如下化 合物。
实施例5(1)
8-(N-丙基-N-(2-甲氧基亚氨基乙基)氨基)-2-甲基-3-(2-甲基-4-甲氧基苯 基)-5,7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.22(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,吡啶-d5 0.5ml+CDCl3 0.1ml):
主要异构体
δ7.87(t,J=5.4Hz,1H),7.38(d,J=8.4Hz,1H),7.03(d,J=2.7Hz,1H), 6.95(dd,J=8.4,2.7Hz,1H),5.27(s,2H),4.97(s,2H),4.59(d,J=5.4Hz,2H),3.86(s, 3H),3.74(s,3H),3.38(t,J=7.5Hz,2H),2.44(s,3H),2.31(s,3H),1.65-1.50(m, 2H),0.81(t,J=7.5Hz,3H).
次要异构体
δ7.38(d,J=8.4Hz,1H),7.31(t,J=4.2Hz,1H),7.03(d,J=2.7Hz,1H), 6.95(dd,J=8.4,2.7Hz,1H),5.25(s,2H),4.95(s,2H),4.71(d,J=4.2Hz,2H),3.92(s, 3H),3.74(s,3H),3.43(t,J=7.2Hz,2H),2.43(s,3H),2.31(s,3H),1.65-1.50(m, 2H),0.84(t,J=7.2Hz,3H).
实施例5(2)
8-(N-乙基-N-正-丁氨基)-2-羟基亚氨基甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf 0.19(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.15(s,1H),7.96(brs,1H),7.18(d,J=8.1Hz,1H), 6.85(d,J=2.7Hz,1H),6.79(dd,J=8.1,2.7Hz,1H),3.82(s,3H),3.67(q,J=7.2Hz, 2H),3.61(t,J=7.5Hz,2H),2.99(t,J=7.2Hz,2H),2.92(t,J=7.8Hz,2H),2.18(s, 3H),2.16(m,2H),1.55(m,2H),1.33(m,2H),1.18(t,J=7.2Hz,3H),0.89(t, J=7.5Hz,3H).
实施例6
8-[(2S)-1-羟基亚氨基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
向实施例2(15)中制备的化合物(290mg)在乙酸(4ml)中的溶液中,加入 1M乙酸(1.4ml),并将该混合物在80℃下搅拌1小时。将该反应混合物倒 入在冰浴下的饱和碳酸氢钠溶液(100ml)中,将所得混合物用乙酸乙酯萃 取。将所得溶液用饱和氯化钠水溶液洗涤,在无水硫酸钠上干燥。将羟胺 盐酸(52mg)加入残余物在吡啶(3ml)中的溶液中。将该混合物在室温下搅拌 15小时。将该反应混合物浓缩并用乙酸乙酯稀释。将该稀释的溶液相继用 饱和碳酸氢钠水溶液和氯化钠饱和溶液洗涤,在无水硫酸钠上干燥。将残 余物在硅胶柱色谱(正己烷∶乙酸乙酯=1∶1)上纯化,得到标题化合物(143 mg),其具有如下物理数据:为异构体混合物。
TLC:Rf0.32(正己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):
主要异构体
δ7.80(brs,1H),7.47(d,J=6.0Hz,1H),7.14(d,J=8.4Hz,1H),6.84(d, J=2.7Hz,1H),6.78(dd,J=8.4,2.7Hz,1H),6.53(d,J=9.6Hz,1H),4.60(m,1H), 3.82(s,3H),3.25-3.00(m,2H),2.88(t,J=7.5Hz,2H),2.31(s,3H),2.17(s,3H), 2.10(m,2H),1.90(m,2H),1.11(t,J=7.2Hz,3H)、
次要异构体
δ8.52(brs,1H),7.14(d,J=8.4Hz,1H),6.84(d,J=2.7Hz,1H),6.80(m,1 H),6.78(dd,J=8.4,2.7Hz,1H),6.44(d,J=9.6Hz,1H),5.23(m,1H),3.82(s,3H), 3.25-3.00(m,2H),2.88(t,J=7.5Hz,2H),2.31(s,3H),2.17(s,3H),2.10(m,2H), 1.90(m,2H),1.11(t,J=7.2Hz,3H).
实施例6(1)
8-[(2S)-1-甲氧基亚氨基丁-2-基]氨基-2-甲基-3-(2-甲基-4-甲氧基苯基)-5, 7-二氢-呋喃并[3,4-d]吡唑并[1,5-a]嘧啶
按照与实施例5的反应相同的工艺,用实施例2(14)中制备的化合物和 邻-甲基羟基胺盐酸代替羟基胺盐酸,获得标题化合物(128mg),其具有如 下物理性能。
TLC:Rf0.20(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):
主要异构体
δ7.36(d,J=6.0Hz,1H),7.14(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.4,2.7Hz,1H),6.60(d,J=9.9Hz,1H),5.47(d,J=10.5Hz,1H),5.31(d, J=10.5Hz,1H),4.89(s,2H),4.07(m,1H),3.86(s,3H),3.82(s,3H),2.33(s,3H), 2.16(s,3H),1.96-1.87(m,2H),1.10(t,J=7.5Hz,3H).
次要异构体
δ7.14(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H),6.79(dd,J=8.4,2.7Hz,1H), 6.76(m,1H),6.53(d,J=9.9Hz,1H),5.30(m,2H),4.89(s,2H),4.72(m,1H),3.96(s, 3H),3.82(s,3H),2.33(s,3H),2.16(s,3H),1.96-1.87(m,2H),1.10(t,J=7.5Hz, 3H).
实施例7
8-[(1S)-1-氰丙氨基]-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
向实施例6中制备的化合物(137mg)在二氯甲烷(1ml)中的冷却至- 78℃的溶液中,加入三乙胺(0.32ml)和三氟甲磺酸酐(0.13ml)。将该混合物 在室温下搅拌2小时。将饱和碳酸氢钠溶液加入反应混合物中,并将所得 溶液用乙酸乙酯萃取。将所得溶液用饱和氯化钠水溶液洗涤,在无水硫酸 钠上干燥。将残余物在硅胶柱色谱(正己烷∶乙酸乙酯=3∶1→2∶1)上纯化,得 到标题化合物(100mg),它具有如下物理数据:
TLC:Rf0.27(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.86(d,J=2.7Hz,1H), 6.79(dd,J=8.1,2.7Hz,1H),6.50(d,J=9.6Hz,1H),4.78(m,1H),3.82(s,3H), 3.33(ddd,J=14.4,7.5,6.3Hz,1H),3.11(ddd,J=14.4,8.1,6.3Hz,1H),2.93(m, 2H),2.31(s,3H),2.25-2.10(m,7H),1.29(t,J=7.5Hz,3H).
实施例7(1)
8-(N-乙基-N-正-丁氨基)-2-氰基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
按与实施例7的反应相同的工艺,用实施例5(2)中制备的化合物(211mg) 获得标题化合物(195mg),其具有如下物理数据:
TLC:Rf0.34(正己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.4Hz,1H),6.88(d,J=2.7Hz,1H), 6.83(dd,J=8.4,2.7Hz,1H),3.83(s,3H),3.65(q,J=6.9Hz,2H),3.58(t,J=7.5Hz, 2H),3.00(t,J=7.2Hz,2H),2.96(t,J=7.8Hz,2H),2.29(s,3H),2.18(m,2H), 1.57(m,2H),1.33(m,2H),1.20(t,J=6.9Hz,3H),0.91(t,J=7.2Hz,3H).
实施例8
9-(3-戊氨基)-6-甲基-5-(2-甲基-4-甲氧基苯基)-呋[3,2-d]吡唑并[1,5-a]嘧 啶
向实施例2(6)中制备的化合物在二苯基醚(3ml)中的溶中,加入10%钯 碳(150mg),并将该混合物在250℃下搅拌4小时。将该反应混合物冷却至 室温后,将其用甲醇(10ml)稀释。将该溶液通过celite(注册商标)过滤。将 滤液浓缩,并将残余物在硅胶柱色谱(正己烷∶丙酮=9∶1)上纯化,得到标题化 合物(150mg),它具有如下物理数据:
TLC:Rf0.42(正己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.76(d,J=2.4Hz,1H),7.20(d,J=8.1Hz,1H), 6.88(d,J=2.7Hz,1H),6.80(dd,J=8.1,2.7Hz,1H),6.78(d,J=2.4Hz,1H),6.28(brd, J=10.2Hz,1H),4.30(m,1H),3.83(s,3H),2.37(s,3H),2.21(s,3H),1.92-1.65(m, 4H),1.05(m,6H).
实施例9
8-(3-戊氧基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
将3-戊醇(202mg)滴加入在甲苯中的氢化钠(92.0mg;60%,在油中)溶 液中,并将该混合物在80℃下搅拌2分钟。将参考例7中制备的化合物(250mg) 加入该混合物中,并将所得混合物搅拌5小时。将水和乙酸乙酯加入反应 混合物中。分离有机层。同时将水层用乙酸乙酯萃取。将合并的有机层用 氯化钠饱和溶液洗涤,在无水硫酸钠上干燥。将残余物在硅胶柱色谱(己烷∶ 乙酸乙酯=5∶1)上纯化,得到标题化合物(128mg),它具有如下物理数据:
TLC:Rf0.58(甲苯∶丙酮=5∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.86(d,J=2.4Hz,1H), 6.79(dd,J=8.4,2.4Hz,1H),5.05(quint,J=6.0Hz,1H),3.82(s,3H),3.05(t, J=7.5Hz,2H),2.94(t,J=7.5Hz,2H),2.34(s,3H),2.22-2.10(m,2H),2.16(s,3H), 1.92-1.78(m,4H),1.05(t,J=7.5Hz,6H).
实施例9(1)-9(5)
按与实施例9的反应相同的工艺,用相应的化合物,制备如下化合物。
实施例9(1)
8-(3-戊氧基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.50(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.4Hz,1H),7.06(d,J=2.4Hz,1H), 6.89(dd,J=8.4,2.4Hz,1H),5.06(quint,J=6.0Hz,1H),3.83(s,3H),3.05(t, J=7.2Hz,2H),2.95(t,J=7.2Hz,2H),2.38(s,3H),2.16(quint,J=7.2Hz,2H),1.94- 1.74(m,4H),1.04(t,J=7.5Hz,6H).
实施例9(2)
8-(3-戊氧基)-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并[3,4-d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.25(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.4Hz,1H),7.07(d,J=2.7Hz,1H), 6.90(dd,J=8.4,2.7Hz,1H),5.29(s,2H),4.93(s,2H),4.56(m,1H),3.84(s,3H), 2.41(s,3H),1.99-1.80(m,4H),1.05(t,J=7.5Hz,6H).
实施例9(3)
8-(4-庚氧基)-2-甲基-3-(2-氯-5-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶
TLC:Rf0.85(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.06(d,J=2.7Hz,1H), 6.89(dd,J=8.7,2.7Hz,1H),5.22(quint,J=6.0Hz,1H),3.83(s,3H),3.05(t, J=7.5Hz,2H),2.95(t,J=7.5Hz,2H),2.37(s,3H),2.16(quint,J=7.5Hz,2H),1.90- 1.66(m,4H),1.58-1.42(m,4H),0.95(t,J=7.2Hz,6H).
实施例9(4)
8-异丙基氧基-2-甲基-3-(2-氯-5-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑 并[1,5-a]嘧啶
TLC:Rf0.36(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.4Hz,1H),7.06(d,J=2.4Hz,1H), 6.89(dd,J=8.4,2.4Hz,1H),5.43(sept,J=6.3Hz,1H),3.83(s,3H),3.06(t,J=7.5Hz, 2H),2.96(t,J=7.5Hz,2H),2.38(s,3H),2.16(quint,J=7.5Hz,2H),1.51(d, J=6.3Hz,6H).
实施例9(5)
8-(1,6-庚二烯-4-基)氧基-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.58(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.4Hz,1H),7.06(d,J=2.7Hz,1H), 6.89(dd,J=8.4,2.7Hz,1H),5.90(ddt,J=17.1,10.2,6.9Hz,2H),5.34(quint, J=6.3Hz,1H),5.17(m,2H),5.11(dd,m,2H),3.83(s,3H),3.01(t,J=7.5Hz,2H), 2.95(t,J=7.5Hz,2H),2.70-2.50(m,4H),2.38(s,3H),2.15(quint,J=7.5Hz,2H).
实施例10
8-(3-戊基硫)-2-甲基-3-(2-氯-5-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡唑并 [1,5-a]嘧啶盐酸
将3-乙酰基硫戊烷(252mg)和参考例7中制备的化合物(300mg)在0℃ 下加入氢化钠(68.9mg;60%,在油中)在乙醇(17ml)中的溶液中。将该反应 混合物搅拌1小时后,将反应混合物浓缩。将水和乙酸乙酯加入残余物中 并搅拌。将有机层分离,同时,用乙酸乙酯萃取水层。将合并的有机层用 饱和氯化钠水溶液洗涤,在无水硫酸钠上干燥。将残余物在硅胶柱色谱(己 烷∶乙酸乙酯=5∶1)上纯化,将4N乙酸-乙酸乙酯(0.2ml)加入纯化的物质 中,将该溶液搅拌10分钟并浓缩,得到标题化合物(271.1mg),它具有如 下物理数据:
TLC:Rf0.57(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.29(d,J=8.7Hz,1H),7.07(d,J=2.4Hz,1H), 6.89(dd,J=8.7,2.4Hz,1H),4.27(quint,J=6.3Hz,1H),3.84(s,3H),3.05(t, J=7.5Hz,2H),3.00(t,J=7..5Hz,2H),2.40(s,3H),2.17(quint,J=7.5Hz,2H), 1.72-1.64(m,4H),1.02(t,J=7.5Hz,6H).
实施例11
8-(4-甲基苯基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
向参考例7中制备的化合物(300mg)在二甲氧基乙烷(3ml)中的溶液中, 加入4-甲基苯基硼酸(131mg),乙酸钯(11mg),三苯基膦(48mg)和碳酸钠饱 和水溶液(2ml),并将该混合物在加热下回流5小时。将反应混合物冷却后, 将该稀溶液用饱和氯化钠溶液和水洗涤,在无水硫酸镁上干燥并浓缩。将 残余物在硅胶柱色谱(己烷∶乙酸乙酯=5∶1)上纯化,得到标题化合物(222 mg),它具有如下物理数据:
TLC:Rf0.41(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.72(d,J=8.1Hz,2H),7.36(d,J=8.1Hz,2H), 7.19(d,J=8.4Hz,1H),6.88(d,J=2.7Hz,1H),6.81(dd,J=2.7,8.4Hz,1H),3.84(s, 3H),3.01(t,J=7.5Hz,2H),2.94(t,J=6.6Hz,2H),2.45(s,3H),2.30(s,3H),2.20(s, 3H),2.14(m,2H).
实施例11(1)-11(5)
按与实施例11的反应相同的工艺,用相应的化合物,制备如下化合物。
实施例11(1)
8-(2,4-二氯苯基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf TLC:Rf0.38(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,DMSO-d6):δ7.91(d,J=1.8Hz,1H),7.70(d,J=8.4Hz,1H), 7.64(dd,J=1.8,8.4Hz,1H),7.11(br d,J=8.1Hz,1H),6.90(d,J=2.7Hz,1H), 6.81(dd,J=2.7,8.4Hz,1H),3.77(s,3H),2.94(m,2H),2.68(m,2H),2.14(s,3H), 2.12(m,2H),2.09(s,3H).
实施例11(2)
8-(3-三氟甲基苯基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.27(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.08(brs,1H),8.06(brd,J=8.1Hz,1H), 7.79(brd,J=7.8Hz,1H),7.70(brdd,J=8.1,7.8Hz,1H),7.19(d,J=8.1Hz,1H), 6.89(d,J=2.7Hz,1H),6.82(dd,J=8.1,2.7Hz,1H),3.84(s,3H),3.04(t,J=7.5Hz, 2H),2.94(t,J=7.5Hz,2H),2.31(s,3H),2.20(s,3H),2.18(m,2H).
实施例11(3)
8-(4-甲氧基苯基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶盐酸
TLC:Rf0.23(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.92(d,J=9.0Hz,2H),7.16(d,J=9.0Hz,2H), 7.16(d,J=9.0Hz,1H),6.92(d,J=2.7Hz,1H),6.86(dd,J=9.0,2.7Hz,1H),3.95(s, 3H),3.85(s,3H),3.61(t,J=7.5Hz,2H),3.09(t,J=7.5Hz,2H),2.38(s,3H), 2.30(m,2H),2.20(s,3H).
实施例11(4)
8-(3,5-二氯苯基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑并[1,5-a]嘧啶
TLC:Rf0.50(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.69(d,J=1.8Hz,2H),7.52(t,J=1.8Hz,1H), 7.17(d,J=8.4Hz,1H),6.88(d,J=2.7Hz,1H),6.82(dd,J=2.7,8.4Hz,1H),3.84(s, 3H),3.02(t,J=7.5Hz,2H),2.93(t,J=6.9Hz,2H),2.32(s,3H),2.19(s,3H),2.17(m, 2H).
实施例11(5)
8-(2-甲基苯基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]吡 唑并[1,5-a]嘧啶
TLC:Rf0.38(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.34-7.48(m,4H),7.20(m,1H),6.89(d,J=2.7Hz, 1H),6.82(dd,J=2.7,8.1Hz,1H),3.84(s,3H),3.04(m,2H),2.81(m,1H),2.62(m, 1H),2.27(s,3H),2.20(m,3H),2.17(s,3H),2.15(m,2H).
实施例12
8-双(乙氧基羰基)甲基-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
将
丙二酸二乙酯(880mg)加入氢化钠(210mg;63.1%,在油中)在四氢 呋喃(10ml)中的悬浮液中,并将该混合物在室温下搅拌30分钟。将参考例 7中制备的化合物(820mg)加入反应混合物中,并将所得混合物在加热下回 流4小时。将饱和氯化铵水溶液(10ml)加入反应混合物中,并将其用乙酸 乙酯萃取。将所得溶液用饱和氯化钠水溶液洗涤,在无水硫酸钠上干燥。 将残余物在硅胶柱色谱(己烷∶乙酸乙酯=8∶1→7∶1)上纯化,得到标题化合物 (1.10g),它具有如下物理数据:
TLC:Rf0.48(己烷∶乙酸乙酯=2∶1);
NMR(300MHz,CDCl3):δ7.15(d,J=8.1Hz,1H),6.87(d,J=3.0Hz,1H), 6.80(dd,J=8.1,3.0Hz,1H),6.02(s,1H),4.32(m,4H),3.82(s,3H),2.96(t, J=7.8Hz,2H),2.91(t,J=7.8Hz,2H),2.32(s,3H),2.21-2.09(m,2H),2.17(s,3 H),1.32(t,J=7.2Hz,6H).
实施例12(1)-12(4)
按照与实施例12的反应相同的工艺,用相应的化合物,制备如下化合 物。
实施例12(1)
8-(1-二甲氨基-1,3-二氧代-2-丁基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6, 7-二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.55(乙酸乙酯);
NMR(300MHz,CDCl3):δ7.14(d,J=8.1Hz,1H),6.87(d,J=1.8Hz,1H), 6.83-6.74(m,1H),6.29(s,1H),3.83(s,3H),3.05(s,3H),3.05-2.60(m,6H),2.41(s, 3H),2.30(s,3H),2.16(brs,6H).
实施例12(2)
8-(2,4-二氧代-3-戊基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[d]吡唑并[1,5-a]嘧啶
TLC:Rf0.34(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ16.93(s,1H),7.19(d,J=8.4Hz,1H),6.89(d, J=3.0Hz,1H),6.83(dd,J=8.4,3.0Hz,1H),3.84(s,3H),3.04(t,J=7.2Hz,2H), 2.81(t,J=7.2Hz,2H),2.33(s,3H),2.20(quint,J=7.2Hz,2H),2.18(s,3H),1.95(s, 6H).
实施例12(3)
8-双(乙氧基羰基)甲基-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
TLC:Rf0.18(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.4Hz,1H),7.07(d,J=2.4Hz,1H), 6.89(dd,J=8.4,2.4Hz,1H),6.02(s,1H),4.40-4.20(m,4H),3.84(s,3H),2.98(t, J=7.5Hz,2H),2.92(t,J=7.5Hz,2H),2.35(s,3H),2.17(quint,J=7.5Hz,2H),1.31(t, J=7.2Hz,6H).
实施例12(4)
8-双(乙氧基羰基)甲基-2-甲基-3-(2-氯-4-甲氧基苯基)-5,7-二氢-呋喃并 [3,4-d]吡唑并[1,5-a]嘧啶
TLC:Rf0.28(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.28(d,J=8.4Hz,1H),7.08(d,J=2.4Hz,1H), 6.91(dd,J=8.4,2.4Hz,1H),6.12(s,1H),5.11(s,2H),4.95(s,2H),4.41-4.20(m, 4H),3.84(s,3H),2.39(s,3H),1.33(t,J=7.2Hz,6H).
实施例13
8-(1,3-羟基-2-丙基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑并[1,5-a]嘧啶
在氩气气氛下,将1M二异丙基氢化铝(3.94ml;在己烷中)滴加入在- 78℃下实施例12中制备的化合物(355mg)在无水乙醚(7ml)中的溶液中。将 该混合物在0℃下温热并搅拌4.5小时。将甲醇滴加入该混合物中,然后在 室温下温热。将1N乙酸加入反应混合物中,并将该混合物用乙酸乙酯萃 取。将所得溶液用饱和氯化钠水溶液洗涤,在无水硫酸钠上干燥。将残余 物在硅胶柱色谱(己烷∶乙酸乙酯=3∶1)上纯化,得到标题化合物(260mg),它 具有如下物理数据:
TLC:Rf0.50(氯仿∶甲醇=9∶1);
NMR(300MHz,CDCl3):δ7.13(brd,J=8.7Hz,1H),6.87(s,1H),6.80(brd, J=8.7Hz,1H),4.97(m,1H),4.90(m,1H),4.24(m,2H),4.13(m,2H),3.83(s,3H), 3.59(m,1H),2.98(brt,J=7.2Hz,4H),2.31(s,3H),2.28-2.00(m,5H).
实施例14
8-(1,3-二甲氧基-2-丙基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H- 环戊[d]吡唑并[1,5-a]嘧啶
将实施例13中制备的化合物(120mg)在DMF(2ml)中的溶液在0℃下 滴加入氢化钠(26.0mg;60%,在油中)在DMF中的溶液中。将甲基碘(81.0μl) 滴加入该混合物中,然后搅拌1小时。将水和乙酸乙酯加入该反应混合物中, 并分离有机层。此外,将水层用乙酸乙酯萃取。将合并的有机层用饱和氯化 钠水溶液洗涤,并在加入苯(5ml)后,在无水硫酸钠上干燥并浓缩。将残余 物在硅胶柱色谱(己烷∶乙酸乙酯=3∶1)上纯化,得到标题化合物(58.7mg),它 具有如下物理数据:
TLC:Rf0.80(乙酸乙酯);
NMR(300MHz,CDCl3):δ7.15(d,J=8.4Hz,1H),6.86(d,J=2.4Hz,1H), 6.79(dd,J=8.4,2.4Hz,1H),4.28-4.16(m,1H),4.14-4.06(m,2H),3.96-3.86(m, 2H),3.83(s,3H),3.35(s,6H),3.06(t,J=7.5Hz,2H),2.94(t,J=7.5Hz,2H),2.31(s, 3H),2.17(s,3H),2.17-2.08(m,2H).
实施例15
8-(N,N-二甲基氨基甲酰基甲基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7- 二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶
向实施例12中制备的混合物(410mg)在甲醇(1ml)中的溶液中,在24 ℃下加入50%二甲胺水溶液(491mg),并将该混合物在90℃下搅拌20小 时。将该反应混合物冷却至室温,将水和乙酸乙酯加入该混合物中并搅拌。 分离有机层。此外,将水层用乙酸乙酯萃取。将合并的有机层用饱和氯化钠 水溶液洗涤,在无水硫酸钠上干燥。将残余物在硅胶柱色谱(己烷∶乙酸乙酯 =5∶1)上纯化,得到标题化合物(102.7mg),它具有如下物理数据:
TLC:Rf0.55(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.87(d,J=2.7Hz,1H), 6.80(dd,J=8.4,2.7Hz,1H),3.83(s,3H),3.27(d,J=1.2Hz,1H),3.04-2.94(m,5H), 2.72(s,3H),2.36(s,3H),2.24-2.10(m,8H).
参考例8
2-氯-4-甲氧基
苯甲醛向氢化钠(2.6g;62.6%,在油中)在二甲基甲酰胺(80ml)中的悬浮液中, 在15分钟内滴加入2-氯-4-羟基苯甲醛(10.0g)在二甲基甲酰胺(50ml)中的 溶液。将该混合物搅拌30分钟。将甲基碘(4.2ml)在0℃下在10分钟内滴 加入该反应混合物中,并搅拌1小时。将该反应混合物倒入水中,并用己 烷/乙酸乙酯(1∶1)萃取。将有机层用水和氯化钠饱和水溶液洗涤,在无水硫 酸镁上干燥并浓缩,得到标题化合物(10.7g),它具有如下物理数据:
TLC:Rf0.61(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ10.33(d,J=0.6Hz,1H),7.90(d,J=9.0Hz,1H), 6.94(d,J=2.4Hz,1H),6.89(ddd,J=9.0,2.4,0.6Hz,1H),3.89(s,3H).
参考例9
1-(2,2-二溴乙烯基)-2-氯-4-甲氧基苯
将四溴化碳加入(10.7g)在参考例8(5.0g)中制备的化合物二氯甲烷中的 溶液中。将三苯基膦(16.9g)分批加入保持内部温度5℃或更低的混合物中。 将该混合物在0℃下搅拌30分钟。将该反应混合物在己烷(500ml)中的悬浮 液倒入硅胶(30g)中,然后过滤。将硅胶用己烷/乙酸乙酯(10∶1)洗涤。将滤 液和洗涤液合并并浓缩。将残余物在硅胶柱色谱(己烷∶乙酸乙酯=10∶1)上纯 化,得到标题化合物(6.6g),它具有如下物理数据:
TLC:Rf0.82(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.62(d,J=9.0Hz,1H),7.51(s,1H),6.94(d, J=2.1Hz,1H),6.83(dd,J=9.0,2.1Hz,1H),3.81(s,3H).
参考例10
1-(1-丙炔基)-2-氯-5-甲氧基苯
向参考例9中制备的化合物(1.98g)在四氢呋喃(20ml)中的溶液中,在- 78℃下加入1.57M正丁基锂在己烷(8.2ml)中的溶液。将该混合物搅拌30 分钟并在0℃下搅拌1小时。将该反应混合物冷却至-78℃,加入甲基碘(0.46 ml)并在0℃下搅拌1小时。将该反应混合物倒入水中并用乙酸乙酯萃取。 将所得溶液用饱和氯化钠水溶液洗涤,在无水硫酸镁上干燥并浓缩。将残余 物在硅胶柱色谱(己烷∶乙酸乙酯=10∶1)上纯化,得到标题化合物(0.89g),它 具有如下物理数据:
TLC:Rf0.69(己烷∶乙酸乙酯=5∶1);
NMR(300MHz,CDCl3):δ7.34(d,J=8.7Hz,1H),6.91(d,J=2.7Hz,1H), 6.73(d,J=8.7Hz,2.7Hz,1H),3.79(s,3H),2.10(s,3H).
参考例11
5-双(三甲基甲硅烷基)氨基-2-氰基-3-甲基-4-(2-氯-4-甲氧基苯基)吡咯
在氩气气氛下,将二异丁基氢化铝(13.8ml)慢慢加入经30分钟加热干 燥的氯化镍(832g)中,然后将该混合物搅拌15分钟。该混合物的
颜色变黑 后,将在参考例10中制备的在三甲基甲硅烷基氰化物(46ml)中的化合物(11.6 g)在20分钟内加入该反应混合物中。将该混合物加热,并蒸出己烷。将溶 液在130℃下搅拌2.5小时。将该反应混合物在室温下冷却,并用二氯甲烷 稀释。将稀释的溶液在硅胶柱色谱(己烷∶乙酸乙酯=10∶1)上纯化,得到标题 化合物(9.5g),其具有如下物理数据:和副产品2-双(三甲基甲硅烷基)氨 基-5-氰基-3-甲基-4-(2-氯-4-甲氧基苯基)吡咯(5.2g)。
TLC:Rf0.34(己烷∶乙酸乙酯=10∶1);
NMR(300MHz,CDCl3):δ7.76(brs,1H),7.10(d,J=8.4Hz,1H),7.00(d, J=2.7Hz,1H),6.82(dd,J=8.4,2.7Hz,1H),3.83(s,3H),2.06(s,3H),0.14(s,9H),- 0.14(s,9H).
参考例12
5-氨基-2-氰基-3-甲基-4-(2-氯-4-甲氧基苯基)吡咯
向参考例11中制备的化合物(6.27g)在甲醇(50ml)中的溶液中,在室温 下加入1N氢氧化钠水溶液(15.4ml)。将该混合物在加热下回流1.5小时。 将该反应混合物冷却至室温后,将该反应混合物倒入碳酸钠水溶液中,并 用乙酸乙酯萃取。将所得溶液用饱和氯化钠水溶液洗涤,在无水硫酸镁上干 燥,并浓缩得到标题化合物(4.78g),它具有如下物理数据:
TLC:Rf0.20(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ8.61(brs,1H),7.14(d,J=8.7Hz,1H),7.03(d, J=2.4Hz,1H),6.86(dd,J=8.7,2.4Hz,1H),3.83(s,3H),3.71(brs,2H),2.04(s, 3H).
实施例16
1-氰基-2-甲基-8-羟基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊 [d]吡唑[1,2-a]嘧啶
用与实施例1的反应相同的工艺,用参考例12中制备的化合物(4.15 g),获得标题化合物(1.35g)。
TLC:Rf0.15(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,DMSO-d6):δ12.25(brs,1H),7.31(d,J=7.8Hz,1H),7.20(d, J=2.7Hz,1H),7.02(dd,J=7.8,2.7Hz,1H),3.83(s,3H),2.83(m,2H),2.66(m,2H), 2.06(s,3H),2.03(m,2H).
实施例17
1-氰基-2-甲基-8-(3-戊氨基)-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑[1,2-a]嘧啶
通过与实施例2的反应相同的工艺,用1-氰基-2-甲基-8-氯-3-(2-氯-4- 甲氧基苯基)-6,7-二氢-5H-环戊[d]吡咯并[1,2-a]嘧啶(180mg)(它通过按与 参考例7的反应相同的工艺,用参考例16中制备的化合物制备),获得获 得标题化合物(112mg)。
TLC:Rf0.36(甲苯∶乙酸乙酯=9∶1);
NMR(300MHz,CDCl3):δ7.25(d,J=8.4Hz,1H),7.05(d,J=2.4Hz,1H), 6.88(dd,J=8.4,2.4Hz,1H),5.94(d,J=9.0Hz,1H),3.83(s,3H),3.82(m,1H), 3.04(m,2H),2.87(m,2H),2.29(s,3H),2.11(m,2H),1.82-1.60(m,4H),1.04(t, J=7.5Hz,3H),1.03(t,J=7.5Hz,3H).
实施例17(1)
1-氰基-2-甲基-8-二丙氨基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d] 吡唑[1,2-a]嘧啶
按照与参考例8→参考例9→参考例10→参考例11→参考例12→实施 例16→实施例17的反应系列相同的工艺,用相应的化合物获得标题化合 物,其具有如下物理数据:
TLC:Rf0.39(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.26(d,J=8.1Hz,1H),7.06(d,J=2.4Hz,1H), 6.89(dd,J=8.1,2.4Hz,1H),3.84(s,3H),3.35-3.13(m,4H),3.00-2.80(m,4H), 2.32(s,3H),2.14(m,2H),1.81-1.38(m,4H),0.91(t,J=7.5Hz,6H).
参考例13
5-氨基-4-氰基-2,3-二甲基-1-(2-甲基-4-甲氧基苯基)吡咯
向2-甲基-4-甲氧基苯胺(10g)在甲苯(120ml)中的溶液中,加入3-羟基- 2-丁酮和对甲苯磺酸水合物(44mg)。将该混合物在加入下回流2小时。将 该反应混合物冷却至室温后,将丙二腈(4.6ml)加入反应混合物中,并将其 加热回流12小时。将该冷却的反应混合物浓缩。将残余物用乙醚稀释,并 过滤得到标题化合物(5.73g),其具有如下物理数据:
TLC:Rf0.65(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.07(d,J=8.4Hz,1H),6.87(d,J=3.0Hz,1H), 6.82(dd,J=3.0,8.4Hz,1H),3.84(s,3H),3.71(brs,2H),2.06(s,3H),1.99(s,3H), 1.73(s,3H).
实施例18
2,3-二甲基-4-氨基-1-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[e]吡咯 并[2,3-b]吡啶
向在参考例13中制备的化合物(4.0g)在苯(40ml)中的溶液中,加入环 戊酮(1.46ml)和对甲苯磺酸水合物(40mg)。将该混合物加热回流并脱水12 小时。经celite过滤除去不溶物质,将滤液浓缩。在氩气气氛下,将2M 二异丙基酰胺锂(15.7ml;在THF中)在0℃下加入残余物在四氢呋喃(80ml) 中的溶液中,然后将该混合物温热至室温,并搅拌5天。将水加入反应混 合物中,并将该混合物用乙酸乙酯萃取。将萃取物相继用水和饱和氯化钠 水溶液洗涤,在无水硫酸镁上干燥并浓缩。将残余物在硅胶柱色谱(乙酸乙 酯)上纯化,得到标题化合物(2.85g),其具有如下物理数据:
TLC:Rf0.51(氯仿∶甲醇=10∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.85(d,J=3.0Hz,1H), 6.80(dd,J=3.0,8.4Hz,1H),4.31(s,2H),3.83(s,3H),2.90(m,2H),2.74(m,2H), 2.48(s,3H),2.10(m,2H),1.97(s,3H),1.90(s,3H).
实施例19
2,3-二甲基-4-乙基羰基氨基-1-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环 戊[e]吡咯并[2,3-b]吡啶
向实施例18中制备的化合物(600mg)在THF(60ml)中的溶液中,加入 三乙胺(520μl)和丙酰氯(180μl)。将该混合物搅拌2小时。将反应混合物用 乙酸乙酯稀释,并将稀释的溶液相继用饱和碳酸氢钠溶液和氯化钠饱和水 溶液洗涤,在无水硫酸镁上干燥并浓缩。将残余物用己烷洗涤,得到标题化 合物(451mg),它具有如下物理数据:
TLC:Rf0.60(氯仿∶甲醇=10∶1);
NMR(300MHz,CDCl3):δ7.30(m,1H),7.08(d,J=8.4Hz,1H),6.87(d, J=2.7Hz,1H),6.83(dd,J=2.7,8.4Hz,1H),3.84(s,3H),2.98(t,J=7.2Hz,2H), 2.87(m,2H),2.51(m,2H),2.37(s,3H),2.09(m,2H),2.02(s,3H),1.88(s,3H), 1.33(m,3H).
实施例20
2,3-二甲基-4-丙氨基-1-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[e]吡 咯并[2,3-b]吡啶
向实施例19中制备的化合物(451mg)在THF(5.0ml)中的溶液中,加 入2M硼烷二甲基硫化物复合物(4.8ml;在THF中),将该混合物加热回流 5小时。将甲醇加入反应混合物中,然后将该混合物加热回流2小时。反 应混合物冷却后,将该混合物用乙酸乙酯稀释。将稀释的溶液用水和氯化 钠饱和水溶液洗涤,在无水硫酸镁上干燥并浓缩。将残余物在硅胶柱色谱(己 烷∶乙酸乙酯=1∶1)上纯化,得到标题化合物(268mg),它具有如下物理数据:
TLC:Rf0.47(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.09(d,J=8.7Hz,1H),6.85(d,J=2.7Hz,1H), 6.80(dd,J=2.7,8.7Hz,1H),3.83(s,3H),3.43(m,2H),3.05(m,2H),2.84(m,2H), 2.48(s,3H),2.04(m,2H),1.97(s,3H),1.90(s,3H),1.65(m,2H),1.02(t,J=7.5Hz, 3H).
实施例21
2,3-二甲基-4-(N-乙基羰基-N-丙氨基)-1-(2-甲基-4-甲氧基苯基)-6,7-二 氢-5H-环戊[e]吡咯并[2,3-b]吡啶
在氩气气氛下,将三乙胺(360μl)和丙酰氯(134μl)在0℃下加入实施例 20中制备的化合物(234mg)在二氯甲烷(3.0ml)中的溶液中。将该混合物 搅拌1小时。将该反应混合物用乙酸乙酯稀释,并将稀释的溶液相继用碳 酸氢钠水溶液、水和氯化钠饱和水溶液洗涤,在无水硫酸镁上干燥并浓缩。 将残余物在硅胶柱色谱(己烷∶乙酸乙酯=2∶1)上纯化,得到标题化合物(242 g),它具有如下物理数据:
TLC:Rf0.57(己烷∶乙酸乙酯=1∶1);
NMR(300MHz,CDCl3):δ7.11(m,1H),6.90(d,J=2.4Hz,1H),6.85(dd, J=2.4,8.4Hz,1H),3.92(m,1H),3.86(s,3H),3.42(m,1H),3.01(t,J=7.8Hz,2H), 2.87(m,2H),2.20(s,3H),1.94-2.20(m,4H),2.05(s,3H),1.92 and 1.90(s,total 3H),1.63(m,2H),0.99-1.10(m,3H),0.85-0.94(m,3H).
实施例22
2,3-二甲基-4-二丙氨基-1-(2-甲基-4-甲氧基苯基)-6,7-二氢-5H-环戊[e] 吡咯并[2,3-b]吡啶
按照与实施例20的反应相同的工艺,用实施例21中制备的化合物(242 mg),获得标题化合物(182mg),其具有如下物理数据:
TLC:Rf0.45(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.87(d,J=2.7Hz,1H), 6.81(dd,J=8.4,2.7Hz,1H),3.84(s,3H),3.17(m,4H),2.95(t,J=7.5Hz,2H), 2.88(t,J=7.5Hz,2H),2.44(s,3H),2.05(m,2H),2.01(s,3H),1.92(s,3H),1.52(m, 4H),0.85(t,J=7.2Hz,6H).
实施例22(1)
2,3-二甲基-4-(N-乙基-N-戊氨基)-1-(2-甲基-4-甲氧基苯基)-6,7-二氢- 5H-环戊[e]吡咯并[2,3-b]吡啶
按照与实施例19→实施例20→实施例21→实施例22的反应系列相同 的工艺,用施例18中制备的化合物和相应化合物,获得标题化合物,其具 有如下物理数据:
TLC:Rf0.41(己烷∶乙酸乙酯=3∶1);
NMR(300MHz,CDCl3):δ7.10(d,J=8.4Hz,1H),6.86(d,J=2.7Hz,1H), 6.81(dd,J=8.4,2.7Hz,1H),3.84(s,3H),3.27(q,J=6.9Hz,2H),3.18(m,2H), 2.95(t,J=7.2Hz,2H),2.88(t,J=7.8Hz,2H),2.44(s,3H),2.05(m,2H),2.00(s,3H), 1.91(s,3H),1.50(m,2H),1.38-1.20(m,4H),1.05(t,J=6.9Hz,3H),0.86(t, J=6.9Hz,3H).
配方实施例
配方实施例1
将如下组分按照常规方法掺混并
冲压,获得各自含50mg活性成份的100 片片剂。
·8-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-
二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶 ……5.0g
·
羧甲基纤维素钙(崩解剂) ……0.2g
·硬脂酸镁2(润滑剂) ……0.1g
·微晶纤维素 ……4.7g
配方实施例2
将如下组分按照常规方法掺混。将溶液按照常规方法消毒,并将5ml 部分放入安瓿并
冷冻干燥,获得各自含20mg活性成份的100个。
·8-(3-戊氨基)-2-甲基-3-(2-甲基-4-甲氧基苯基)-6,7-
二氢-5H-环戊[d]吡唑并[1,5-a]嘧啶 ……2.0g
·甘露糖醇 ……20g
·蒸馏水 ……500ml