化药合成,抗肿瘤新药(14)

ethyl ether);FAB-MS m/e317(M+1);UV k max356,341, 304,272,235,205nm;IR(KBr):3026,2945,1731,1622, 1335,1242cmÀ1;1H NMR(500MHz,CDCl3):8.89–8.90(2H,d,J=4Hz,H-4,H-1),8.21–8.22(1H,d, J=8Hz,H-8),7.58–7.61(1H,m,H-5),7.47–7.48(1H,d, J=8.5Hz,H-6),7.35–7.38(1H,m,H-7),7.24–7.28(3H, m,Ar–H),7.13–7.15(2H,m,Ar–H),5.60(2H,s,C H2Ar), 4.05(3H,s,OC H3).Anal.Calcd for C20H16N2O2:C, 75.95;H,5.06;N,8.86.Found:C,75.75;H,5.29;N,8.78.

4.1.16.Ethyl9-methyl-b-carboline-3-carboxylate(6a).A mixture of6(2.4g,10mmol)and anhydrous DMF (60mL)was stirred at rt for10min,then60%NaH (0.6g,15mmol)and iodomethane(2mL,30mmol)were ter the mixture was treated in a manner similar to that described for5a to a?ord white crystals6a(1.9g, 75%),mp139–140°C(from ethyl ether);FAB-MS m/e 255(M+1);UV k max358,342,306,272,236,219nm; IR(KBr):3446,3398,2603,1721,1628,1328, 1280cmÀ1;1H NMR(500MHz,CDCl3):8.94(1H,s, H-4),8.86(1H,s,H-1),8.19–8.20(1H,d,J=7.5Hz,H-8),7.66–7.67(1H,m,H-5),7.49–7.51(1H,d,J=8.5Hz, H-6),7.35–7.37(1H,m,H-7), 4.52–4.56(2H,m, OC H2CH3), 3.98(3H,s,NC H3), 1.48–1.51(3H,s, OCH2C H3).Anal.Calcd for C15H14N2O2:C,70.87;H,

5.51;N,11.02.Found:C,70.73;H,5.73;N,11.09.

4.1.17.Ethyl9-ethyl-b-carboline-3-carboxylate(6b).A mixture of6(2.4g,10mmol)and anhydrous DMF (60mL)was stirred rt for10min,then60%NaH (0.6g,2mmol)and iodoethane(2.5mL,30mmol)were ter the mixture was treated in a manner simi-lar to that described for5a to a?ord white crystals6b (1.8g,67%),mp117–118°C(from ethyl ether);FAB-MS m/e269(M+1);UV k max359,344,306,273,237, 221nm;IR(KBr):3413,2984,1717,1633,1334, 1257cmÀ1;1H NMR(500MHz,CDCl3):8.93(1H,s, H-4),8.86(1H,s,H-1),8.18–8.21(1H,d,J=8Hz,H-8),7.62–7.64(1H,m,H-5),7.48–7.50(1H,d,J=8Hz, H-6),7.33–7.36(1H,m,H-7), 4.42–4.56(4H,m, OC H2CH3,NC H2CH3),1.46–1.52(6H,m,OCH2C H3, NCH2C H3).Anal.Calcd for C16H16N2O2:C,71.64; H,

5.97;N,10.45.Found:C,71.41;H,

6.21;N,10.38.

4.1.18.Ethyl9-butyl-b-carboline-3-carboxylate(6c).A mixture of6(2.4g,10mmol)and anhydrous DMF (60mL)was stirred rt for10min,then60%NaH (0.6g,15mmol)and n-butyl iodide(6mL,50mmol)were added and re?uxed ter the mixture was trea-ted in a manner similar to that described for5a to a?ord white crystals6c(2.3g,78%),mp76–77°C(from petro-leum ether–ethyl ether1:2);FAB-MS m/e297(M+1); UV k max359,343,307,273,235,221nm;IR(KBr): 3438,2956,1731,1623,1333,1242cmÀ1;1H NMR (500MHz,CDCl3):8.98(1H,s,H-4),8.89(1H,s,H-1),8.21–8.23(1H,d,J=8Hz,H-8),7.63–7.66(1H,m, H-5),7.51–7.53(1H,d,J=8.5Hz,H-6),7.36–7.38(1H, m,H-7),4.52–4.56(2H,m,OC H2CH3),4.42–4.44(2H, m,C H2CH2CH2CH3), 1.88–1.94(2H,m,CH2C H2-CH2CH3), 1.49–1.52(3H,m,OCH2C H3), 1.35–1.42 (2H,m,CH2CH2C H2CH3),0.93–0.96(3H,m,CH2CH2-CH2C H3).Anal.Calcd for C18H20N2O2:C,72.97;H, 6.76;N,9.46.Found:C,72.78;H,6.98;N,9.37.4.1.19.Ethyl9-benzyl-b-carboline-3-carboxylate(6d).A mixture of5(2.4g,10mmol)and anhydrous DMF (60mL)was stirred rt for10min,then60%NaH(0.6g, 2mmol)and benzyl bromide(5mL,40mmol)were added and re?uxed ter the mixture was treated in a manner similar to that described for5a to a?ord white crystals6d(2.4g,70%),mp126–127°C(from ethyl ether);FAB-MS m/e331(M+1);UV k max356,342,305, 273,234nm;IR(KBr):3425,3060,3027,2974,1723, 1622,1335,1214cmÀ1;1H NMR(500MHz,CDCl3): 8.91(2H,m,H-4,H-1),8.23–8.25(1H,d,J=8Hz,H-8),7.59–7.62(1H,m,H-5),7.49–7.50(1H,d,J=8Hz, H-6),7.36–7.39(1H,m,H-7),7.25–7.27(3H,s,Ar–H), 7.14–7.16(2H,m,Ar–H),

5.62(2H,s,C H2Ar),4.51–4.55(2H,m,OC H2CH3),1.47–1.50(3H,m,OCH2C H3). Anal.Calcd for C21H18N2O2:C,7

6.36;H,5.45;N,8.48. Found:C,76.19;H,5.67;N,8.38.

4.1.20.Ethyl9-(20,30,40,50,60-penta?uoro)benzyl-b-carbo-line-3-carboxylate(6e).A mixture of5(2.4g,10mmol) and anhydrous DMF(60mL)was stirred at rt for 10min,then60%NaH(0.6g,15mmol)and a-bromo-2,3,4,5,6-penta?uorotoluene(3mL,20mmol)were ter the mixture was treated in a manner simi-lar to that described for5a to a?ord white crystals6d (2.6g,62%),mp153–154°C(from ethyl ether);FAB-MS m/e421(M+1);UV k max350,335,299,271,236, 217nm;IR(KBr):3399,3065,2987,1709,1627,1337, 1245cmÀ1;1H NMR(500MHz,CDCl3):9.07(1H,s, H-4),8.86(1H,s,H-1),8.19–8.21(1H,d,J=8Hz,H-8),7.65–7.68(1H,m,H-5),7.59–7.61(1H,d, J=8.5Hz,H-6),7.38–7.41(1H,m,H-7),

5.67(2H,s, C H2Ar),4.52–4.56(2H,m,OC H2CH3),1.49–1.51(3H, m,OCH2C H3).Anal.Calcd for C21F5H13N2O2:C, 60.00;H,3.10;N,

6.6

7.Found:C,59.87;H,3.29;N, 6.5

8.

4.1.21.Ethyl9-phenylpropyl-b-carboline-3-carboxylate (6f).A mixture of5(2.4g,10mmol)and anhydrous DMF(60mL)was stirred at rt for10min,then60% NaH(0.6g,2mmol)and1-bromo-3-phenylpropane (6mL,40mmol)were added and re?uxed ter the mixture was treated in a manner similar to that de-scribed for5a to a?ord white crystals6e(2.0g,56%), mp140–142°C(from ethyl ether);FAB-MS m/e359 (M+1);UV k max358,343,306,273,236,217nm;IR (KBr):3026,2983,2933,1724,1622,1333,1246cmÀ1; 1H NMR(500MHz,CDCl

搜索“diyifanwen.net”或“第一范文网”即可找到本站免费阅读全部范文。收藏本站方便下次阅读，第一范文网，提供最新教学研究化药合成,抗肿瘤新药(14)全文阅读和word下载服务。