CN114085216B 一类烯基吲哚衍生物的合成方法 （兰州大学）

JiaLi,etal..C-HAlkenylatio卷7742-7746.2R2为吲哚2-7位取3[0002]烯基吲哚化合物具有重要的药理活性，如1956,)、抗炎作用、抗真菌作用(JournalofPharmacy，5,459-462)、抗疟疾作用烯基吲哚衍生物由于其分子中存在不饱和双键结构，不仅能通过与不同的亲双烯体发生Diels-Alder反应构建出不同的四氢咔唑结构，还可发生Pauson-Khand反应和烯烃的交叉[0003]目前合成烯基吲哚化合物的主要合成方法包括：吲哚3位发生wittig反应和临基[0007]MasahiroMiura等报道了钯催化的吲哚-3-羧酸与烯烃的氧化乙烯基化反应，实4到。5120.54,120.26,114.38,111.49,50.98,30.11,27.79,25.06.℃下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3(10mL)淬灭，并用[0028]实施例2所得产品(E)-2-(2-(2-(tert-butyI)-1,3-dithian-2-yl)vinyl)-3-123.76,122.79,120.61,120.38,114.82,111.53,66.77,40.38,27.52,26.18,25.64.[0033]实施例3所得产品(E)-3-(2-(2-(tert-butyl)-1,3-dithian-2-yl)vinyl)-1H-6123.76,122.79,120.61,120.38,114.82,111.53,66.77,40.38,27.52,26.18,25.64.[0036]实施4：制备(E)-3-((1,5-dithiaspiro[5.5]undecan-7-y0.03mmol)，在-20℃下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3113.54,111.16,56.71,41.38,27.84,27.47,26.90,26.14,22.10.[0042]实施5：制备((E)-3-((1,5-dithiaspiro[5.5]undecan-7-methyl-1H-indole方法的反应甲基吲哚(33mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟(10.6mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO37[0044]实施例5所得产品((E)-3-((1,5-dithiaspiro[5.5]undecan-7-ylidene)26.87,26.16,22.14,21.64.[0047]实施6：制备(E)-3-((1,5-dithiaspiro[5.5]undecan-7-ylidene)methyl)-5-methoxy-1H-indole方法的反应甲氧基吲哚(37mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟(10.6mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3[0049]实施例6所得产品(E)-3-((1,5-dithiaspiCNMR(101MHz,CDCl3)δ154.42,140.47,130.98,1227.02,26.20,22.20.[0052]实施7：制备(E)-3-((1,5-dithiaspiro[5.5]undecan-7-ylidene)methyl)-5-溴基吲哚(49mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟(10.6mg，80.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO326.12,22.11.[0058]实施8：制备(E)-3-((1,5-dithiaspiro[5.5]undecan-7-ylidene)methyl)-2-methyl-1H-indole方法的反应甲基吲哚(33mg，0.25mmol)[0060]实施例8所得产品(E)-3-((1,5-dithiaspi26.23,22.08,12.89.[0063]实施9：制备(E)-3-((1,5-dithiaspiro[5.5]undecan-7-ylidene)methyl)-2-9苯基吲哚(48mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟(10.6mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3128.87,128.66,128.54,128.24,127.85,127.72,126.92,123.03,110.61,60.24,28.85,24.71.13CNMR124.28,122.81,120.64,120.35,114.34,111.50,59.87,28.91,24.76.[0075]实施11：制备(E)-5-chloro-3-(2-(2-phenyl-1,3-dithian-2-yl)vinyl)-1H-CNMR(101MHz,DMSO)δ(E-isomer)142.51,135.87,128.98,128.64,128.36,128.34,127.94,127.06,126.57,124.90,122.18,118.70,114.03,112.27,59.57,28.69,24.57.[0081]实施12：制备(E)-4-bromo-3-(2-(2-phenyl-1,3-dithian-2-yl)vinyl)-1H-℃下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3(10mL)淬灭，并用CNMR(101MHz,CDCl3)δ(E-isomer)141.89,137.44,129.75,128.81,24.80.[0087]实施13：制备(E)-5-nitro-3-(2-(2-phenyl-1,3-dithian-2-yl)vinyl)-1H-拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3(10mL)淬灭，并用EtOAc142.32,141.59,140.43,129.90,129.64,129.05,128.59,128.49,126.10,124.87,117.60,116.37,114.85,112.96,59.33,28.67,24.53.134.68,128.85,128.48,128.36,127.86,126.91,126.57,121.83,120.51,119.68,110.60,110.58,109.84,60.23,28.91,24.76,12.34.[0100]实施15：制备(E)-2-phenyl-3-(2-(2-phenyl-1,3-dithian-2-yl)vinyl)-1H-128.66,128.54,128.24,127.85,127.72,126.92,123.03,121.00,120.77,111.27,110.61,60.24,28.85,24.71.[0108]实施例17所得产品(E)-3-(2-(2-(p-tolyl)-1,3-dithian-2-yl)vinyl)-1H-24.79,21.14.[0112]在25毫升圆底烧瓶中，加入4-甲氧基苯基-阝-氯-乙烯-1，3-二噻烷(29mg，0.2mmol)和3-甲基吲哚(57mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟24.72.HNMR(400MHz,Chloroform-d)δ8.16(s,1H),7.92–7.82(m,3H),7.3128.67,127.50,125.44,124.45,122.86,120.70,120.30,115.37,115.16,114.15,111.55,59.23,28.93,24.63.19FNMRdihydro-4H-pyrrolo[3,2,1-ij]quino[0124]在25毫升圆底烧瓶中，加入4-甲氧基苯基-阝-氯-乙烯-1，3-二噻烷(57mg，(15x3mL)重新萃取水相，用盐水(15x3mL)洗涤合并的有机提取物，并在无水Na2SO4上干127.99,127.87,126.56,123.52,122.11,120.67,119.50,118.22,113.68,112.93,59.47,55.35,44.24,29.04,24.81,24.71,22.82.[0129]实施21：制备(E)-3-methyl-2-(2-(2-phenyl-1,3-dithian-2-yl)vinyl)-1H-CNMR(101MHz,CDCl3)δ141.40,136.45,130.89,129.46,128.64,128.62,128.13,123.36,122.88,119.58,119.10,112.82,110.53,59.23,28.78,24.54,8.81.0.03mmol)，在30℃下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3133.98,130.63,130.23,129.41,128.90,128.71,123.49,123.12,119.63,119.14,113.14,110.50,58.66,28.73,24.35,8.81.搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3(10mL)淬灭，并用EtOAc(m,2H).13CNMR(101MHz,CDCl3123.58,123.21,122.32,119.71,119.23,113.24,110.58,58.80,28.80,24.42,8.90.搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3(10mL)淬灭，并用EtOAc133.23,132.99,130.94,129.52,129.41,128.55,128.44,128.04,127.58,126.64,126.52,126.34,123.47,123.07,119.65,119.18,113.02,110.57,59.42,28.83,24.56,8.91.[0154]实施26：制备(E)-3-methyl-2-(2-(2-methyl-1,3-dithian-2-yl)vinyl)-1H-123.17,120.49,119.52,119.02,112.25,110.50,50.51,29.93,27.69,24.80,8.83.0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3CNMR(101MHz,CDCl3)δ(E-isomer)172.00,136.15,132.68,130.20,128.69,123.87,123.41,120.21,119.06,110.67,108.27,65.87,52.14,40.48,30.33,27.35,26.13,25.33.3-乙酸基吲哚(35mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟(10.6mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3136.75,133.34,130.18,128.74,124.10,122.71,119.30,119.05,111.20,108.18,66.12,30.38,27.03,26.29,25.29.CNMR(101MHz,CDCl3)δ136.47,132.57,129.39,128.91,123.98,123.34,119.90,118.92,112.16,110.68,65.92,63.19,40.51,27.74,27.36,26.11,25.27.6,7,8,9,11,12,13,14,15,16-decahydrospiro[cyclopenta[a]phenanthrene-17,2'-[0181]实施例30所得产品(8R,9S,13S,14S,E)-16-((1H-indol-3-yl)methylene)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydrospiro[cyclopenta[a]phenanthrene-17,CNMR(101MHz,CDCl3)δ153.42,142.41,138.16,135.42,132.60,127.24,126.45,122.58,122.43,119.90,119.08,117.38,115.33,114.55,112.78,111.01,67.28.48,28.36,27.94,26.76,24.65,17.43.(4.4mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，[0186]实施例31所得产品(E)-N-(2-(2-(2-(2-(tert-butyl)-1,3-dithian-2-yl)HNMR(400MHz,Chloroform-d)δ8.26.13,25.26,24.25,23.43.methoxy-1H-indol-3-yl)ethyl)acetamide方法的反应[0191]实施例32所得产品(E)-N-(2-(2-(2-(2-(tert-butyl)-1,3-dithian-2-yl)25.22,24.23,23.43.酰-L-色氨酸(62mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入TEMPO(4.7mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3[0197]实施例33所得产品(S,E)-2-acetamido-3-(2-(2-(2-(tert-butyl)-1,3-120.20,118.87,110.86,109.71,65.82,53.23,40.59,27.40,26.60,26.19,25.23,23.12.L-色氨酸(62mg，0.25mmol)，用6毫升1,2-二氯乙烷溶解后加入三溴化铟(10.6mg，0.03mmol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，混合物用1NNaHCO3136.57,132.78,131.16,128.96,128.72,128.23,123.60,122.01,120.11,119.01,110.93,110