一种手性含亚胺噁唑啉胺类的化合物及其制备方法_3

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.9Hz,lH) ,7.34 (ddd ,J = 9.8,8.8,2.1Hz,2H),7.00-6.94(m,lH),4.38(dd ,J = 9.4,8.1Hz,lH),4.21-4.11 (m,lH),4.05(t,J = 8.1Hz,lH),1.82(dq,J=13.4,6.7Hz,lH),1.02(d,J = 6.7Hz,3H) ,0.94 (d,J = 6.7Hz,3H) .13C 匪R(101MHz,CDC13) :δ190·4,162.6,143.1,142.3,134.7,133.1, 131.5,130.3,125.7,125.2,120.7,119.9,117.4,115.2,76.7,73.1,69.3,33.1,18.8, 18.7.HRMS(EI)calculated for[Ci9HigClN202]+requires m/z 342.1135,found m/z 356.1139.
[0087] 实例A6:化合物A6的制备
[0088]
[0089] 氮气保护下,(S)-2-(4-异丙基-4,5-二氢噁唑-2-基)苯胺(2.24738,11!11111〇1, 1 · lequiv)与2_溴_4_氣苯甲酸(2.0300g, lOmmol, 1 .Oequiv)在20mL二氧六环中,Pd(dba)2 (0.2875g,0.5mmol, 5mol % ) ,Xantphos(0.3472g,0.6mmol,6mol % ),碳酸钟(2 · 7642g, 20mmol,2.06 911;^),200<€反应30分钟,石油醚:乙酸乙酯=20:1过柱,得到3.0355区 (9.3mmol,93 % )含噁唑啉胺类的化合物A6。
[0090] 咕 NMR(400MHz,CDCl3):Sll.57(s,lH),9.98(s,lH),7.87(dd,J=7.9,1.6Hz,lH), 7.65(dd,J = 8.6,6.6Hz,lH),7.55(d,J = 8.3Hz,lH) ,7.44-7.34(m,lH),7.17(dd,J= 12.0, 2.3Hz,lH) ,7.03(t ,J = 7.6Hz,lH) ,6.64(td ,J = 8.2,2.3Hz , 1H) ,4.37(dd ,J = 9.4,8.1Hz , 1H) ,4.22-4.10(m,lH),4.05(t,J = 8.1Hz,lH) ,1.83(dd,J=13.4,6.7Hz,lH) ,1.03(d,J = 6.7Hz,3H) ,0.94(d,J = 6.7Hz,3H).13C NMR(101MHz,CDC13) :δ190.6,168.4,165.9,162.2, 147.3,147.2,143.3,141.1,138.0,137.9,134.8,131.4,130.5,130.4,129.0,128.4, 125 · 5,121 · 7,120 · 4,120 · 4,119 · 1,116 · 7,107 · 4,107 · 1,102 · 9,102 · 6,73 · 2,69 · 4,33 · 1, 18.8,18.6.HRMS(EI)calculated for[Ci9Hi9FN202]+requires m/z 326.1432,found m/z 356.1434.
[0091] 实例A7:化合物A7的制备
[0092]
[0093]氮气保护下,(S)-2-(4-异丙基-4,5-二氢噁唑-2-基)苯胺(2.24738,11!11111〇1, 1 · lequiv)与 2-溴-4-甲基苯甲酸(2.0300g, lOmmol, 1 · Oequi v)在20mL 二氧六环中,Pd (dba)2(0.2875g,0.5mmol,5mol % ),Xantphos (0 · 3472g,0 · 6mmol,6mol % ),碳酸钟 (2 · 7642g,20mmol,2 · Oequiv),30°C反应48小时,石油醚:乙酸乙酯=20 :1过柱,得到 3.0950g(9.6mmol,96% )含噁唑啉胺类的化合物A7。
[0094] 4 匪R(400MHz,CDC13) :Sll.32(s,lH),10.04(s,lH),7.84(dd,J = 7.9,1.5Hz, lH),7.60(dJ = 7.9Hz,lH),7.50(d,J = 8.3Hz,lH),7.33(dt,J = 8.5,2.3Hz,2H),7.01-6.87(m,lH),6.82(d ,J = 7.9Hz,lH) ,4.37(dd ,J = 9.4,8.1Hz , 1H) ,4.21-4.09(m, 1H) ,4.04 (t,J = 8.1Hz,lH) ,2.33(s,3H),1.82(dd,J=13.4,6.7Hz,lH),1.03(d,J = 6.7Hz,3H) ,0.94 (d,J = 6.7Hz,3H) .13C 匪R(101MHz,CDC13) :δ191·3,162·5,146·0,144·7,142·7,134·5, 131.3,130.3,122.6,121.6,120.2,118.1,117.9,115.2,73·2,69·3,33·1,22.1,18.9, 18.6.HRMS(El) calculated for[C20H22N202]+requires m/z 322.1681, found m/z 322.1677.
[0095] B)含亚胺噁唑啉胺类的化合物B的制备
[0096] 实例B1:亚胺噁唑啉胺B1的制备
[0097]
[0098] 2,6-二异丙基苯胺(1.337(^,7.5111111〇1,1.2691^¥)与厶1(2.0538 8,5.8111111〇1, 1 · Oequiv)溶于12mL甲苯中,对甲苯横酸(0 · 0998g,0 · 58mmol,10mol % )催化,反应48h,乙醇 重结晶得到 1 · 9978g(3 · 9mmo 1,67 % )B1。
[0099] 4 NMR(400MHz,CDCl3):Sl0.81(s,lH),8.44(s,lH),8.06(d,J = 8.0Hz,lH),7.75 (d,J = 8.0Hz,lH),7.47(d,J = 5.6Hz,2H),7.29-7.15(m,5H),7.15-7.01(m,6H),6.77(t,J = 7.5Hz,lH),4.52-4.41(m,lH),4.16(t ,J = 8.8Hz,lH),3.98(t ,J = 7.7Hz,lH),3.02-2.89 (m,3H),2.51(dd,J = 13.6,9.2Hz,lH),1.19-1.01(m,12H) .13C 匪R(101MHz,CDC13) :δ 163.8.160.7.149.6.146.0. 142.5.137.9.137.7.131.9.131.9.130.1.129.9.129.2, 129.0. 128.4.126.4.124.0.123.9.123.6.122.9.118.0.114.8.112.0.70.3.67.9.41.7, 27.9,23.5,23.5.HRMS(EI)calculated for[C35H37N30]+requires m/z 515.2937,found m/ z 515.2937.
[0100] 实例B2:亚胺噁唑啉胺B2的制备
[0101]
[0102] 2,6-二异丙基苯胺(1.1525区,6.5111111〇1,1.36911;[¥)与八2(1.5420区,51]1111〇1, 1 ·Oequiv)溶于15mL甲苯中,对甲苯横酸(0 ·0430g,0 · 25mmol,5mol % )催化,反应48h,乙醇 重结晶得到 1.3431g(2.9mmol,57%)B2。
[0103] 4 NMR(400MHz,CDCl3):Sl0.73(s,lH),8.45(s,lH),8.13(d,J = 7.5Hz,lH),7.75 (dd J = 7.9,1.4Hz,lH),7.51-7.41(m,2H),7.30-7.16(m,2H),7.15-6.98(m,4H),6.76(t ,J =7.5Hz,lH),4.30-4.18(m,lH),4.07-3.94(m,2H),3.02-2.88(m,2H),1.72-1.60(td,J= 13.1,6.6Hz,lH),1.09(t ,J = 6.4Hz,12H),0.84(d ,J = 6.8Hz,3H),0.75(d ,J = 6.8Hz,3H) .13C NMR(101MHz,CDCl3)Jl63.3,160.4,149.6,146.3,142.4,137.7,132.0,131.8,130.0, 129.6.129.4.124.5.124.0. 123.9.122.9.117.7.114.4.111.7.72.5.68.5.32.6.27.9, 23.5,23.4,18.9,17.9.HRMS(EI)calculated for[C3iH37N30]+requires m/z 467.2937, found m/z 467.2934.
[0104] 实例B3:亚胺噁唑啉胺B3的制备
[0105]
[0106] 2,6-二异丙基苯胺(3.546〇8,2〇111111〇1,1.36 911;[¥)与厶3(5.31798,15.51]1111〇1, 1. Oequiv)溶于30mL甲苯中,对甲苯横酸(0.2580g,1.5mmol,lOmol % )催化,反应48h,乙醇 重结晶得到 5.9603g(11.8mmol,76%)B3。
[0107] 4 NMR(400MHz,CDCl3):Sl0.74(s,lH),8.40(s,lH),8.05(d,J = 7.6Hz,lH),7.85 (d,J = 7.6Hz,lH) ,7.45(d,J = 4.0Hz,2H) ,7.30-7.20(m,3H),7.15(s,4H) ,7.10-7.02(m, 4H) ,6.80(t ,J = 7.5Hz,lH),5.39-5.27(m,lH),4.69-4.59(m,lH) ,4.08(t ,J = 8.0Hz , 1H), 2.88(dt,J=13.6,6.8Hz,2H) ,1.04(d,J = 6.8Hz,6H),0.98(d,J = 6.8Hz,6H) .13C 匪R (101MHz,CDCl3):Sl64.8,160.6,149.7,146.5,142.4,137.7,132.3,132.0,130.4,129.8, 129.4.128.7.127.5.126.4.124.5.124.1.123.9.123.0. 118.0.114.9.111·7,73·4,70·1, 27.9,23.5,23.4;HRMS(EI)calculated for[C34H35N30]+requires m/z 501.2780,found m/ z 501.2777.
[0108] 实例M:亚胺噁唑啉胺M的制备
[0109]
[0110] 2,6-二异丙基苯胺(1.1525区,6.5111111〇1,1.36911;[¥)与八4(1.6120区,51]1111〇1, 1 · Oequiv)溶于10mL甲苯中,对甲苯横酸(0 · 043g,0 · 25mmol,5mol % )催化,反应48h,乙醇重 结晶得到 1 · 7256g(3 · 6mmo 1,71 % )B4。
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