CN115403591A - 一种合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法 - Google Patents
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
本发明公开了一种合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，属于有机合成技术领域。以异喹啉酮类化合物1和1‑重氮萘‑2(1H)‑酮类化合物2为起始原料，在铑催化剂和氧化剂存在下，通过氧化环化反应得到萘并噻吩并奥塞平并异喹啉酮类化合物3。本发明具有起始原料简单易制备、底物范围广、操作步骤简单等优点。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法。
背景技术
奥塞平并异喹啉酮是一类非常重要的含七元环稠杂环结构。苯氧西平含有奥塞平骨架，广泛存在于药用植物中，该类化合物在药物研发方面具有十分重要的意义。例如：Heliannuol C是一种天然产物，因其具有独特的含奥塞平骨架，而表现出较强的抗生素活性且在药物研究领域展现出良好的应用前景。
然而，由于含奥塞平稠杂环骨架合成方法的匮乏，从而在很大程度上制约了该类化合物的发展。因此，非常有必要开发一种实用合成奥塞平稠杂环化合物的方法。
发明内容
本发明解决的技术问题是提供了一种起始原料简单易制备、底物适用范围广且操作简单的高效合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法。
本发明所述合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，包括如下步骤：以异喹啉酮类化合物1和1-重氮萘-2(1H)-酮类化合物2为原料，在铑催化剂和氧化剂存在下，有机溶剂中升温反应，得到萘并噻吩并奥塞平并异喹啉酮类化合物3。采用反应方程式表示如下：
其中：R1为H、C1-C4烷基、CF3，R2为H、C1-C4烷基，R3为H、C1-C4烷基、C1-C4烷氧基、卤素、苯基、萘基。
进一步地，在上述技术方案中，所述铑催化剂为[Cp*RhCl2]2。
进一步地，在上述技术方案中，所述氧化剂为AgOAc或Ag2O。
进一步地，在上述技术方案中，所述有机溶剂为N,N-二甲基甲酰胺、1,4-二氧六环、甲苯或N,N-二甲基乙酰胺。
进一步地，在上述技术方案中，所述异喹啉酮类化合物1、1-重氮萘-2(1H)-酮类化合物2、铑催化剂与氧化剂摩尔比为1:1.0-2.0:0.01-0.025:1.5-2.0。
进一步地，在上述技术方案中，反应温度为80-120℃。
相比现有文献方法，本发明合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，具有起始原料简单易制备、底物适用范围广等优点。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物升温至100℃加热搅拌3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)得到化合物3a(32mg,43％)。1H NMR(DMSO-d6,600MHz)δ11.75(s,1H),8.43(d,J＝7.8Hz,1H),8.25(d,J＝7.2Hz,1H),8.15(d,J＝8.4Hz,1H),8.08-8.06(m,2H),8.02(d,J＝7.8Hz,1H),7.94-7.91(m,1H),7.84(d,J＝9.0Hz,1H),7.71(d,J＝5.4Hz,1H),7.64-7.60(m,2H),7.56-7.54(m,1H)；13CNMR(DMSO-d6,100MHz)δ161.4,158.0,137.1,136.6,133.8,133.2,132.6,132.0,131.3,131.2,130.4,129.1,128.2,128.0,126.1,125.8,125.4,123.4,122.0,121.3(three 13Csignals were not observed).HRMS(ESI)calcd for C23H13NNaO2S[M+Na]+390.0559,found390.0546.
实施例2
按实施例1所述方法，在15mL耐压管中依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、醋酸银(66.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h，得到化合物3a(19.1mg,26％)。
实施例3
按实施例1所述方法，在15mL耐压管中依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、1,4-二氧六环(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物于100℃加热搅拌反应3h，得到化合物3a(27.2mg,37％)。
实施例4
按实施例1所述方法，在15mL耐压管中依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、甲苯(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h，得到化合物3a(16.9mg,23％)。
实施例5
按实施例1所述方法，在15mL耐压管中依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、N,N-二甲基乙酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h，得到化合物3a(27.2mg,37％)。
实施例6
在15mL耐压管中，依次加入7-甲基-3-(噻吩-2-基)异喹啉-1(2H)-酮1b(48.3mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3b(25mg,33％)。1H NMR(DMSO-d6,600MHz)δ11.66(s,1H),8.32(d,J＝8.4Hz,1H),8.15(d,J＝9.0Hz,1H),8.07-8.05(m,3H),8.02(d,J＝7.8Hz,1H),7.81(d,J＝9.0Hz,1H),7.74(dd,J＝7.8,1.2Hz,1H),7.70(d,J＝5.4Hz,1H),7.62-7.59(m,1H),7.56-7.53(m,1H),2.49(s,3H)；13CNMR(DMSO-d6,100MHz)δ161.3,158.0,137.9,136.8,135.1,132.0,131.3,131.1,130.9,130.4,129.1,128.00,127.95,127.6,126.1,125.4,123.4,122.1,121.3,21.5(four 13Csignals were not observed).HRMS(ESI)calcd for C24H15NNaO2S[M+Na]+404.07 16,found 404.0714.
实施例7
在15mL耐压管中，依次加入3-(噻吩-2-基)-7-(三氟甲基)异喹啉-1(2H)-酮1c(59.1mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝5:1)，得黄色固体3c(26mg,30％)。1H NMR(DMSO-d6,600MHz)δ12.12(s,1H),8.63(d,J＝8.4Hz,1H),8.46(s,1H),8.17-8.13(m,3H),8.09(d,J＝9.0Hz,1H),8.03(d,J＝7.8Hz,1H),7.85(d,J＝9.0Hz,1H),7.73(d,J＝5.4Hz,1H),7.63-7.61(m,1H),7.56(t,J＝7.2Hz,1H)；13C NMR(DMSO-d6,150MHz)δ160.8,157.8,137.9,136.0,132.1,131.4,131.3,130.6,129.6,129.2,129.1,128.1,127.7,127.5,126.2,125.4,125.3,125.1,123.6,123.5,123.2,121.1；19F NMR(DMSO-d6,564MHz)δ-60.99(s).HRMS(ESI)calcd for C24H12F3NNaO2S[M+Na]+458.0433,found 458.0431.
实施例8
在15mL耐压管中，依次加入3-(5-甲基噻吩-2-基)异喹啉-1(2H)-酮1d(48.3mg,0.2mmol)、1-重氮萘-2(1H)-酮2a(68.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3d(29mg,38％)。1H NMR(CDCl3,400MHz)δ8.62(s,1H),8.39(d,J＝7.6Hz,1H),8.29(d,J＝8.0Hz,1H),8.21(d,J＝8.4Hz,1H),7.88-7.81(m,3H),7.58-7.45(m,4H),7.34(d,J＝0.8Hz,1H),2.70(d,J＝0.8Hz,3H)；13C NMR(CDCl3,150MHz)δ161.5,157.8,140.8,137.8,136.8,133.7,133.3,131.9,131.6,130.5,129.5,129.3,128.5,128.4,127.3,127.1,125.6,125.5,125.3,123.5,121.4,120.9,15.8(one 13C signal was not observed).HRMS(ESI)calcdfor C24H15NNaO2S[M+Na]+404.0716,found 404.0717.
实施例9
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-7-甲基萘-2(1H)-酮2b(73.7mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3e(22mg,29％)。1H NMR(CDCl3,400MHz)δ9.94(s,1H),8.43(d,J＝7.6Hz,1H),8.31(d,J＝8.0Hz,1H),7.97(s,1H),7.86-7.81(m,2H),7.75(d,J＝8.4Hz,1H),7.68(m,2H),7.58-7.54(m,1H),7.51(d,J＝8.8Hz,1H),7.30(dd,J＝8.0,0.8Hz,1H),2.49(s,3H)；13C NMR(DMSO-d6,150MHz)δ161.4,158.2,137.5,137.3,133.8,133.2,131.6,130.9,130.4,130.2,130.1,129.0,128.24,128.21,128.0,124.4,122.7,122.0,120.3,22.2(four 13C signals werenot observed).HRMS(ESI)calcd for C24H15NNaO2S[M+Na]+404.0716,found 404.0718.
实施例10
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-7-甲氧基萘-2(1H)-酮2c(80.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝2:1)，得棕色固体3f(30mg,38％)。1H NMR(CDCl3,400MHz)δ9.95(s,1H),8.43(d,J＝7.2Hz,1H),8.32(d,J＝8.0Hz,1H),7.87-7.82(m,1H),7.79(d,J＝8.8Hz,1H),7.75(d,J＝8.8Hz,1H),7.72(d,J＝5.2Hz,1H),7.68(d,J＝5.2Hz,1H),7.59-7.53(m,2H),7.44(d,J＝8.8Hz,1H),7.13(dd,J＝8.8,2.4Hz,1H),3.88(s,3H)；13C NMR(DMSO-d6,150MHz)δ161.4,158.9,158.8,137.4,133.8,133.2,132.9,130.9,130.8,129.9,128.4,128.0,127.4,122.4,122.0,118.7,118.3,104.4,55.5(five 13C signals were not observed).HRMS(ESI)calcd forC24H15NNaO3S[M+Na]+420.0665,found 420.0657.
实施例11
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-7-溴萘-2(1H)-酮2d(99.6mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3g(37mg,41％)。1H NMR(CDCl3,600MHz)δ10.27(s,1H),8.44(d,J＝7.8Hz,1H),8.35(s,1H),8.29(d,J＝8.4Hz,1H),7.86-7.82(m,2H),7.72-7.71(m,2H),7.63(d,J＝5.4Hz,1H),7.60-7.56(m,2H),7.54(dd,J＝9.0,1.8Hz,1H)；13C NMR(DMSO-d6,150MHz)δ161.4,158.7,136.3,133.8,133.1,132.6,131.34,131.29,130.5,130.0,129.1,128.8,128.1,128.0,127.3,122.8,122.0,121.7(five 13C signals were not observed).HRMS(ESI)calcd forC23H12BrNNaO2S[M+Na]+467.966 4,found 467.9662.
实施例12
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-6-甲基萘-2(1H)-酮2e(73.7mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物于100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3h(36mg,47％)。1H NMR(CDCl3,400MHz)δ10.59(s,1H),8.44(d,J＝8.0Hz,1H),8.31(d,J＝8.0Hz,1H),8.07(d,J＝8.8Hz,1H),7.83(t,J＝8.0Hz,1H),7.75(d,J＝8.8Hz,1H),7.66-7.62(m,2H),7.60(s,1H),7.57-7.52(m,2H),7.31(d,J＝8.0Hz,1H),2.47(s,3H)；13C NMR(CDCl3,100MHz)δ162.4,157.4,137.8,137.6,135.1,133.8,133.2,132.2,131.9,130.7,129.8,129.4,128.3,127.5,127.4,126.0,125.63,125.58,125.4,123.3,121.5,120.7,21.3(one 13C signal was not observed).HRMS(ESI)calcd for C24H15NNaO2S[M+Na]+404.0716,found 404.0712.
实施例13
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-6-苯基萘-2(1H)-酮2f(98.5mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3i(21mg,23％)。1H NMR(DMSO-d6,400MHz)δ11.75(s,1H),8.44(d,J＝8.0Hz,1H),8.35(d,J＝1.2Hz,1H),8.23(t,J＝8.4Hz,2H),8.15(d,J＝9.2Hz,1H),8.09(d,J＝5.2Hz,1H),7.96-7.91(m,2H),7.87(d,J＝8.8Hz,1H),7.82(d,J＝7.6Hz,2H),7.74(d,J＝5.2Hz,1H),7.63(t,J＝8.0Hz,1H),7.52(t,J＝8.0Hz,2H),7.41(t,J＝7.6Hz,1H)；13C NMR(DMSO-d6,100MHz)δ161.4,158.0,139.7,137.5,137.0,133.9,133.2,132.4,131.6,130.5,130.4,129.6,128.4,128.3,128.0,127.3,126.9,126.4,126.2,123.3,122.0,121.8(five 13Csignals were not observed).HRMS(ESI)calcd for C29H17NNaO2S[M+Na]+466.0872,found466.0867
实施例14
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-6-(4-苯基)萘-2(1H)-酮2g(104.1mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3j(31mg,34％)。1H NMR(DMSO-d6,600MHz)δ11.78(s,1H),8.44(d,J＝7.8Hz,1H),8.30(s,1H),8.27(d,J＝7.8Hz,1H),8.19(d,J＝9.0Hz,1H),8.12(d,J＝9.0Hz,1H),8.09(d,J＝5.4Hz,1H),7.95-7.90(m,2H),7.85(d,J＝9.0Hz,1H),7.74(d,J＝5.4Hz,1H),7.70(d,J＝7.8Hz,2H),7.64(t,J＝7.8Hz,1H),7.31(d,J＝7.8Hz,2H),2.36(s,3H)；13C NMR(DMSO-d6,150MHz)δ161.4,157.9,137.6,137.4,137.1,136.8,133.8,133.2,132.4,131.5,130.37,130.35,130.1,128.3,128.0,127.1,126.8,126.2,125.9,123.3,122.0,121.7,21.2(five 13C signals were not observed).HRMS(ESI)calcd for C30H19NNaO2S[M+Na]+480.1029,found 480.1 012.
实施例15
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、5-重氮-[2,2'-联萘]-6(5H)-酮2h(118.5mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得黄色固体3k(34mg,34％)。1H NMR(DMSO-d6,600MHz)δ11.78(s,1H),8.48(d,J＝1.2Hz,1H),8.44(d,J＝7.8Hz,1H),8.37(s,1H),8.27-8.23(m,2H),8.17(d,J＝9.0Hz,1H),8.10-8.07(m,2H),8.03(t,J＝8.4Hz,2H),7.99(dd,J＝8.4,1.2Hz,1H),7.96-7.92(m,2H),7.87(d,J＝9.0Hz,1H),7.75(d,J＝4.8Hz,1H),7.63(t,J＝7.8Hz,1H),7.57-7.52(m,2H)；13C NMR(DMSO-d6,100MHz)δ161.4,158.1,137.2,137.04,136.99,133.8,133.2,132.9,132.5,131.6,130.6,130.4,129.1,128.7,128.4,128.0,127.03,127.01,126.8,126.7,126.3,126.0,125.5,123.4,122.0,121.8(seven 13C signals were not observed).HRMS(ESI)calcd for C33H20NO2S[M+H]+494.1209,found 494.1190.
实施例16
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、1-重氮-6-溴-萘-2(1H)-酮2i(99.6mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3l(28mg,32％)。1H NMR(DMSO-d6,400MHz)δ11.75(s,1H),8.42(d,J＝8.4Hz,1H),8.32(d,J＝2.0Hz,1H),8.24(d,J＝8.0Hz,1H),8.09-8.05(m,3H),7.94-7.89(m,2H),7.71(dd,J＝9.2,2.4Hz,1H),7.68(d,J＝5.2Hz,1H),7.63(t,J＝7.2Hz,1H)；13C NMR(DMSO-d6,150MHz)δ161.4,158.2,136.51,136.47,133.8,133.3,133.1,130.81,130.79,130.4,130.3,130.0,128.5,128.1,128.0,127.95,127.89,123.8,122.6,122.0,119.3(two 13C signals werenot observed).HRMS(ESI)calcd for C23H12BrNNaO2S[M+Na]+467.9664,found 467.9669.
实施例17
在15mL耐压管中，依次加入3-(噻吩-2-基)异喹啉-1(2H)-酮1a(45.5mg,0.2mmol)、4-溴-1-重氮-萘-2(1H)-酮2j(99.6mg,0.4mmol)、N,N-二甲基甲酰胺(2mL)、双环戊二烯基二氯化铑(3.1mg,0.005mmol)、氧化银(92.7mg,0.4mmol)，反应管密封，然后将该混合物100℃加热搅拌反应3h。反应完成后，饱和碳酸氢钠淬灭，二氯甲烷萃取，饱和食盐水洗涤，无水硫酸钠干燥。旋干硅胶柱层析分离(石油醚/乙酸乙酯＝3:1)，得棕色固体3m(36mg,40％)。1H NMR(DMSO-d6,400MHz)δ11.80(s,1H),8.51(d,J＝8.0Hz,1H),8.34(s,1H),8.25(d,J＝7.6Hz,1H),8.22-8.17(m,2H),8.10(d,J＝4.8Hz,1H),7.96-7.92(m,1H),7.72-7.68(m,3H),7.66-7.62(m,1H)；13C NMR(DMSO-d6,150MHz)δ161.4,157.1,136.3,133.9,133.0,131.9,130.5,130.1,128.9,128.6,128.1,128.0,127.9,127.5,126.4,125.3,123.9,123.8,122.2(four 13C signals were not observed).HRMS(ESI)calcd forC23H12BrNNaO2S[M+Na]+467.9664,found 467.9669.
以上实施例描述了本发明的基本原理、主要特征及优点，本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。
Claims (6)
1.一种合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，其特征在于，包括如下步骤：以异喹啉酮类化合物1和1-重氮萘-2(1H)-酮类化合物2为原料，在铑催化剂和氧化剂存在下，有机溶剂中升温反应，得到萘并噻吩并奥塞平并异喹啉酮类化合物3；采用反应方程式表示如下：
其中：R1为H、C1-C4烷基、CF3，R2为H、C1-C4烷基，R3为H、C1-C4烷基、C1-C4烷氧基、卤素、苯基、萘基。
2.根据权利要求1所述合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，其特征在于：所述铑催化剂为[Cp*RhCl2]2。
3.根据权利要求1所述合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，其特征在于：所述氧化剂为AgOAc或Ag2O。
4.根据权利要求1所述合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，其特征在于：所述有机溶剂为N,N-二甲基甲酰胺、1,4-二氧六环、甲苯或N,N-二甲基乙酰胺。
5.根据权利要求1所述合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，其特征在于：所述异喹啉酮类化合物1、1-重氮萘-2(1H)-酮类化合物2、铑催化剂与氧化剂摩尔比为1:1.0-2.0:0.01-0.025:1.5-2.0。
6.根据权利要求1-5任意一项所述合成萘并噻吩并奥塞平并异喹啉酮类化合物的方法，其特征在于：反应温度为80-120℃。
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| US20060224007A1 (en) * | 2005-03-31 | 2006-10-05 | Eastman Kodak Company | Synthesis of organometallic cyclometallated transition metal complexes |
| WO2009123971A1 (en) * | 2008-03-31 | 2009-10-08 | Genentech, Inc. | Benzopyran and benzoxepin pi3k inhibitor compounds and methods of use |
| AU2015258280A1 (en) * | 2011-01-10 | 2015-12-10 | Infinity Pharmaceuticals Inc. | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
| US20190127330A1 (en) * | 2017-11-01 | 2019-05-02 | National Taiwan Normal University | Method for Preparing Indenoisoquinoline Derivatives |
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| US20060224007A1 (en) * | 2005-03-31 | 2006-10-05 | Eastman Kodak Company | Synthesis of organometallic cyclometallated transition metal complexes |
| WO2009123971A1 (en) * | 2008-03-31 | 2009-10-08 | Genentech, Inc. | Benzopyran and benzoxepin pi3k inhibitor compounds and methods of use |
| CN102333779A (zh) * | 2008-03-31 | 2012-01-25 | 吉宁特有限公司 | 苯并吡喃和苯并氧杂*pi3k抑制剂化合物和使用方法 |
| AU2015258280A1 (en) * | 2011-01-10 | 2015-12-10 | Infinity Pharmaceuticals Inc. | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
| US20190127330A1 (en) * | 2017-11-01 | 2019-05-02 | National Taiwan Normal University | Method for Preparing Indenoisoquinoline Derivatives |
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