3,4-二氢香豆素类化合物及其制备方法和用图_2

文档序号:9769653阅读:来源:国知局
三个或四个氢原子分别被指定范围的基团中选出的相同或不同的基团替换。
【具体实施方式】
[0078] 下面通过实例来具体说明本发明的I以及II式中化合物的制备方法。这些实例仅 对本发明进行说明,而不对本发明进行限制。
[0079] 实施例1
[0080]化合物I-I 3_(4_甲氧苯甲酰氨基)_2_氧代_4-(苯乙炔基)色满-3-羧酸乙酯的制 备
[0082] 在室温下,原料邻羟基苄醇A(44 · 8mg,0 · 2mmol),1 · 5当量的吖内酯B(78 · 9mg, 0·3mmol),10.Omol%的磷酸二苯酯(5mg,0.Olmmol)溶于无水二氯甲烧中,用TLC检测反应 直到反应完全,以V?S?/Vzi?i=15 :1-5:1柱层析直接得到式I-I目标产物,产率为84%。在 实施例1中,邻羟基苄醇A为2-( 1-羟基-3-苯基丙-2-炔-1-基)苯酚。
[0083] 1H NMR(600MHz,CDCl3)5(ppm)5 = 7.89(d,J = 7.4Hz,2H),7.75(s,lH),7.60(dJ = 8.1Hz,lH),7.46(d ,J = 6.5Hz,2H),7.35(t ,J = 7.3Hz,4H),7.21(t ,J = 7.3Hz,lH),7.13(d, J = 8.2Hz,lH) ,6.97(d J = 8.5Hz,2H),5.65(s,lH),4.26-4.20(m,lH),4.06-4.01(m,lH), 3.87(s,3H),0.90(t ,J = 7.1Hz,3H)〇
[0084] 13C 匪 R(100MHz, CDCl3) δ (ppm) δ = 166.10,165.25,162.90,162.11,150.29, 131.80,129.29,129.04,128.75,128.35,127.35,124.97,124.80,122.07,120.80,116.26, 113.87,86.93,82.69,65.13,63.58,55.41,36.86,13.42。
[0085]高分辨:计算值:[M+H]+: 470 · 1598;实测值:470 · 1595 ·
[0086] 实施例2
[0087]化合物1-2 3_(4_甲氧苯甲酰氨基)_2_氧代_4-(对甲苯基乙炔基)色满-3-羧酸乙 酯的制备
[0089] 根据实施例1的制备方法,将邻羟基苄醇A换为2-(1_羟基_3-(对甲苯基)丙-2-炔_ 1-基)苯酚,其他条件不变,得到式1-2目标产物,产率为85 %。
[0090] 1H NMR(600MHz,CDCl3)5(ppm)5 = 7.88(d,J = 8.7Hz,2H),7.74(s,lH),7.60(dJ = 7.6Hz,lH),7.34(d ,J = 7.8Hz,3H),7.20(d ,J = 7.5Hz,lH),7.16-7.09(m,3H),6.95(s,2H), 5.62(s,lH) ,4.25-4.20(m,lH),4.04-4.00(m,lH) ,3.86(s,3H) ,2.36(s,3H) ,0.89(t J = 7.1Hz,3H)〇
[0091] 13C NMR(100MHz, CDCl3) δ (ppm) δ = 166.03,165.21,162.84,162.14,150.23, 138.94,129.26,129.05,128.97,127.37,124.95,124.76,120.90,118.95,116.19,113.82, 87.03,81.91,65.12,63.53,55.39,36.85,21.43,13.40。
[0092]高分辨:计算值:[M+Na]+: 506.1576,实测值:506.1566.
[0093] 实施例3
[0094]化合物1-3 4-((对氯苯基)乙炔基)-3-(4_甲氧苯甲酰氨基)-2_氧代色满-3-羧酸 乙酯的制备
[0096] 根据实施例1的制备方法,将邻羟基苄醇A换为2-(3-(4_氯苯基)-1_羟基丙-2-炔-1 -基)苯酚,其他条件不变,得到式1-3目标产物,产率为80 %。
[0097] 1H NMR(400MHz,CDCl3)5(ppm)5 = 7.85(d,J = 8.8Hz,2H),7.69(s,lH),7.54(dJ = 7.6Hz,lH) ,7.38-7.22(m,5H),7.17(t,J = 7.5Hz,lH) ,7.09(d,J = 8.1Hz,lH) ,6.93(d J = 8.8Hz,2H) ,5.64(s,lH) ,4.24-4.16(m,lH) ,4.05-3.97(m, 1H), 3.84( s , 3H), 0.88(t J = 7.1Hz,3H)〇
[0098] 13C NMR(100MHz, CDCl3) δ (ppm) δ = 165.81,164.94,162.66,161.77,150.03, 134.67,132.86,129.12,128.97,128.54,127.07,124.69,120.37,120.34,116.20,113.75, 85.80,83.73,65.05,63.66,55.48,36.96,13.60。
[0099]高分辨:计算值:[M+Na]+: 526 · 1028,实测值:526 · 1035。
[0100] 实施例4
[0101] 化合物1-4 4-((3_氟苯基)乙炔基)-3-(4-甲氧苯甲酰氨基)-2_氧代色满-3-羧酸 乙酯的制备
[0103] 根据实施例1的制备方法,将邻羟基苄醇A换为2-(3-(3_氟苯基)-1_羟基丙-2-炔-1-基)苯酚,其他条件不变,得到式1-4目标产物,产率为81 %。
[0104] 1H NMR(600MHz,CDCl3)5(ppm)5 = 7.89(d,J = 8.6Hz,2H),7.73(s,lH),7.57(dJ = 7.7Hz,lH) ,7.36(t,J = 7.8Hz,lH) ,7.32-7.29(m,lH) ,7.24-7.20(m,2H) ,7.14(t,J = 8.5Hz,2H),7.07(t ,J = 8.6Hz,lH),6.97(d ,J = 8.6Hz,2H),5.66(s,lH),4.25-4.20(m,lH), 4.07-4.01(m,lH),3.87(s,3H),0.90(t ,J = 7.1Hz,3H)〇
[0105] 13C NMR(100MHz ,CDCl3) δ (ppm) δ = 165.79,164.87,162.63,161.92 (d, J = 244.9Hz),160.70,149.99,129.84(d ,J = 8.52Hz),129.07,128.97,127.54,127.53(d J = 2.79Hz) ,124.68,124.63,123.59 (d, J= 10.04Hz) ,120.26,118.43 (d, J = 22.59Hz), 116.15,115.92,113.72,85.62,83.68,64.99,63.65,55.42,36.87,13.55。
[0106] 高分辨:计算值:[M+Na]+:510.1323,实测值:510.1328。
[0107] 实施例5
[0108]化合物1-5 4-(环丙基乙炔基)-3-(4-甲氧基苯甲酰氨基)-2-氧代色满-3-羧酸乙 酯的制备
[0110] 根据实施例1的制备方法,将邻羟基苄醇A换为2-(3-环丙基-1-羟基丙-2-炔-1-基)苯酚,其他条件不变,得到式1-5目标产物,产率为79 %。
[0111] 1H NMR(600MHz,CDCl3)5(ppm)5 = 7.87(d,J = 8.4Hz,2H),7.64(s,lH),7.49(dJ = 7.6Hz,lH),7.31(t ,J = 7.7Hz,lH),7.18(t ,J = 7.5Hz,lH),7.07(d ,J = 8.1Hz,lH),6.98(d, J=8.3Hz,2H),5.32(s,lH),4.20-4.14(m,lH),4.02-3.97(m,lH),3.88(s,3H),1.30-1.27 (m, 1H) ,0·88(t,J = 7· IHz,3H),0.83-0.80(m,2H),0.69-0.66(m,2H)。
[0112] 13C 匪R(100MHz,CDCl3) δ (ppm) δ = 141.46,136.59,131.08,130.60,128.44, 127.59,127.53,126.78,126.53,82.47,63.96,15.31〇
[0113] 高分辨:计算值:[M+Na]+: 456.1418,实测值:456.1417。
[0114] 实施例6
[0115] 化合物1-6 3-(4_甲氧基苯甲酰氨基)-2_氧代-4-((三甲基硅基)乙炔基)色满-3-羧酸乙酯的制备
[0117] 根据实施例1的制备方法,将邻羟基苄醇A换为2-(1_羟基_3-(三甲基硅基)丙-2-炔-1 -基)苯酚,其他条件不变,得到式1-6目标产物,产率为80 %。
[0118] 1H NMR(400MHz,CDCl3)S(ppm)S = 7.87(d,J = 8.8Hz,2H),7.69(s,lH),7.51(d,J = 7.6Hz,lH),7.33(t,J = 7.7Hz,lH),7.19(t,J = 7.5Hz,lH),7.09(d,J = 8.0Hz,lH),6.98(d, J = 8.8Hz,2H),5.39(s,lH),4.22-4.17(m,lH),4.02-3.96(m,lH),3.88(s,3H),0.89(t J = 7.1Hz,3H),0.20(s,9H)〇
[0119] 13C NMR(100MHz, CDCl3) δ (ppm) δ = 165.73,164.74,162.63,161.84,149.97, 129.10,128.81,127.13,124.83,124.64,120.34,116.06,113.74,99.12,92.13,64.87, 63·48,55·46,37·15,13·52,-0·03。
[0120]高分辨:计算值:[M+Na]+: 488 · 1500,实测值:488 · 1505 ·
[0121] 实施例7
[0122] 化合物1-7 4-(4_乙炔基苯基)-3-(4_甲氧苯甲酰氨基)-2_氧代色满-3-羧酸乙酯 的制备
[0124] 根据实施例1的制备方法,将邻羟基苄醇A换为2_( (4-乙炔基苯基)(羟基)甲基)苯 酚,其他条件不变,得到式1-7目标产物,产率为82 %。
[0125] 1H NMR(600MHz,CDCl3)S(ppm)S = 7.77(d,J = 8.7Hz,2H),7.47(d,J = 8.2Hz,2H), 7.35-7.32(m,lH),7.23(s,lH),7.18(d,J = 8.0Hz,lH),7.07(d,J = 8.2Hz,3H),6.95(d,J = 8.7Hz,2H),6.90(d,J=7.6Hz,lH),5.68(s,lH),4.18-4.12(m,lH),4.10-4.05(m,lH),3.87 (s,3H),3.13(s,lH),1.04(t ,J = 7.2Hz,3H)〇
[0126] 13C NMR(100MHz, CDCl3) δ (ppm) δ = 165.63,165.33,162.57,162.15,151.05, 135.66,132.21,129.94,128.95,128.59,128.17,127.51,124.81,124.20,122.31,116.41, 113.76,82.76,78.28,66.49,63.66,55.47,47.34,13.51。
[0127] 高分辨:计算值:[M+Na]+: 492.1418,实测值:492.1418.
[0128] 实施例8
[0129] 化合物1-8 3-(4_甲氧基苯甲酰氨基)-2_氧代-4_(噻吩-2-基)色满-3-羧酸乙酯 的制备
[0131 ]根据实施例1的制备方法,将邻羟基苄醇A换为2_(羟基(噻吩-2-基)甲基)苯酚,其 他条件不变,得到式1-8目标产物,产率为83 %。
[0132] 1H NMR(400MHz,CDCl3)S(ppm)S = 7.77(d,J = 8.8Hz,2H),7.37(s,lH),7.29(t,J = 5.2Hz,2H),7.13-7.04(m,3H),7.00(dd ,J = 5.1,3.5Hz,lH),6.93-6.91(m,2H),6.88(d J = 2.9Hz,lH),5.95(s,lH),4.16-4.07(m,2H),3.84(s,3H),0.99(t,J=7.1Hz,3H)〇
[0133] 13C NMR(100MHz, CDCl3) δ (ppm) δ = 165.72,165.32,162.57,162.00,150.50, 136.74,129.03,128.76,128.69,127.49,126.79,126.08,124.99,124.25,123.11,116.17, 113.75,66.85,63.73,55.48,43.33。
[0134] 高分辨:计算值:[M+Na]+: 474.0982,实测值:474.0970。
[0135] 实施例9
[0136] 化合物1-9 4-环己基-3_(4-甲氧基苯甲酰氨基)-2_氧代色满-3-羧酸乙酯的制备
[0138] 根据实施例1的
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