CN113735832B - Preparation method of 7-succinimidyl indole compound - Google Patents
Preparation method of 7-succinimidyl indole compound Download PDFInfo
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Abstract
The invention discloses a preparation method of a 7-succinimide indole compound, which comprises the following steps: in TFE solvent with [ RhCp ] Cl 2 ] 2 As catalyst, agSbF 6 And silver oxide as additive with maleimidoThe amine compound and the indole compound are used as substrates to synthesize the 7-succinimidyl indole compound. The invention has the advantages of cheap and easily obtained reaction raw materials, simple preparation method and simple operation. The method can be used for synthesizing a series of 7-succinimidyl indole compounds, and the synthesized products have great pharmaceutical activity potential, and can be used as intermediate compounds for further constructing other types of active compounds.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a rhodium-catalyzed method for preparing 7-succinimidyl indole compounds.
Background
Succinimides are a very important class of compounds in macromolecular compound synthesis, and their derivatives are widely distributed in natural products and clinical drug candidates. In addition, succinimides can be readily reduced to five-membered ring pyrrolidines, gamma lactams and endo lactams, which are present as dominant backbones in many classes of natural product molecules. Thus, the synthesis of succinimide derivatives has been extensively studied by synthetic chemists. Transition metal catalyzed activation of hydrocarbon bonds is considered a direct, efficient method of constructing carbon-carbon bonds. Over the past few decades, based on this strategy, a process for the direct synthesis of succinimide derivatives by hydroarylation coupling of maleimide and (hetero) aromatic hydrocarbons has been greatly developed.
Indole parent nuclei are widely distributed as the dominant backbone in natural products and pharmaceutically active molecules, and are considered to be the most attractive class of nitrogen-containing heterocycles. The transition metal catalyzed functionalization of hydrocarbon bonds can directly and efficiently construct new carbon-carbon bonds and carbon heteroatom bonds. In the last decades, a number of transition metal catalyzed processes have been developed for the synthesis of substituted indoles. Because of the higher reactivity of the pyrrole ring moiety than the benzene ring moiety, most reported methods are used to synthesize 2-substituted and 3-substituted indoles. Direct regioselective functionalization of the indole benzene ring moiety remains a challenge to synthetic chemists.
7-substituted indoles have a very important role in synthetic chemistry and pharmaceutical chemistry due to their high presence in natural products and bioactive compounds. In 2010, the Hartwig group reported for the first time a regioselective approach to seven-position functionalization at the indole carbon. They control the regioselectivity of the reaction by using diethyl silicon base as a locating group, and realize the synthesis of 7-boron indole catalyzed by iridium. Subsequently, by using different transition metal catalysts (rhodium, iridium, palladium) and appropriate directing groups, various methods of direct functionalization of the seven positions of the indole carbon were established, including alkenylation, arylation, sulphonamidation, alkynylation, acylation and alkylation. In 2018, the Yu research group reported for the first time a rhodium-catalyzed direct carbo-hepta succinimidation of indolines, which were prepared by reduction of the corresponding indoles. Subsequently, the Ravikumar group developed a novel method for synthesizing 7-succinimidyl indoline by cobalt-catalyzed indoline and maleimide coupling. The synthesized 7-succinimidyl indoline needs to be further oxidized to be converted into corresponding 7-succinimidyl indoline. However, no method for synthesizing 7-succinimidyl indole by direct regioselective hydroarylation of the seven positions of indole carbon has been reported. Thus, it is particularly important and urgent to develop a process for regioselective coupling of the seven indoles to the maleimide direct hydroarylation. The establishment of the method not only has important significance and value in synthetic chemistry; meanwhile, the comprehensive research on the biological activity of the 7-succinimidyl indole compounds is further promoted, and new pharmaceutically active compounds are discovered.
Disclosure of Invention
The invention provides a method for preparing a liquid crystal display by [ RhCp ] Cl 2 ] 2 As catalyst, agSbF 6 And silver oxide as additive and maleimide and indole as material. The method has the advantages of easily available raw materials and simple preparation method.
A preparation method of 7-succinimidyl indole compounds comprises the following steps: in a solvent with [ RhCp ] Cl 2 ] 2 As catalyst, agSbF 6 And silver oxide as additive, maleimide and indole react at 80 deg.c, and after the reaction, post-treatment is performedObtaining the 7-succinimidyl indole compound;
the structure of the 7-succinimidyl indole compound is shown in any one of formulas (I) to (VI):
in the formula (I), R 1 Is hydrogen, C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, C 1 ～C 4 Alkanoyloxy or halogen.
The structure of the indole compound is shown in any one of formulas (VII) to (IX):
in the formula (VII), R 1 Is hydrogen, C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, acyloxy or halogen.
The maleimide compound has a structure represented by any one of chemical formulas (X) to (XI):
in the formula (X), R 2 Is cyclohexyl, C 1 ～C 4 Alkyl or benzyl.
Preferably, the catalyst is [ RhCp ] Cl 2 ] 2 Other types of catalysts, including ruthenium and iridium catalysts, reduce the reaction yield or produce no product.
The additive is AgSbF 6 And silver oxide, other types of additives, including salts, oxides, and acids, all reduce reaction yields or produce no product.
The molar ratio of the indole compound to the maleimide compound is as follows: 1:3 to increase the yield of the reaction. Reducing the amount of maleimide decreases the reaction yield.
The indole compound and the catalyst [ RhCp ] Cl 2 ] 2 Additive AgSbF 6 And silver oxide in a molar ratio of 1:0.05:0.2:2 to increase the yield of the reaction. Reducing the amount of catalyst and additives reduces the reaction yield.
Preferably, the reaction solvent is TEF (trifluoroethanol), and other solvents, including other polar solvents and nonpolar solvents, reduce the reaction yield or produce no product.
In the present invention, the reaction temperature is preferably 80 ℃.
The synthetic reaction equation is:
preferably, R 1 Is hydrogen, methyl, methoxy, pivaloyloxy, fluoro or chloro.
The possible principles of the synthesis reaction are: [ RhCp ] Cl 2 ] 2 With AgSbF 6 And silver oxide to produce active cations. The active cation coordinates with the indolyl pivaloyl oxygen, and the rhodium-containing six-membered ring intermediate is generated through hydrocarbon bond activation. The maleimide is inserted into a carbon-rhodium bond of the rhodium-containing six-membered ring intermediate to generate a double-ring intermediate. The bicyclic intermediate is demetallised by proton to give the final product 7-succinimidyl indole.
Compared with the prior art, the invention has the following advantages:
the method takes indole and maleimide as raw materials, and synthesizes the 7-succinimidyl indole compound through direct regioselective indole carbon seven-position hydrogen arylation. The reaction raw materials are cheap and easy to obtain, and the preparation method is simple; by [ RhCp ] Cl 2 ] 2 As catalyst, agSbF 6 And silver oxide is used as an additive, and the reagent is easy to obtain. The reaction is carried out in an air atmosphere, so that the operation is simple. The method can be suitable for synthesizing 7-succinimidyl indole compounds of different types.
Detailed Description
The present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
Example 1
N-pivaloyl indole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were each added to a 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 3 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 45.4mg of the product in 60% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.67(d,J＝3.3Hz,1H),7.54(d,J＝7.7Hz,1H),7.28(t,J＝7.5Hz,1H),7.06(d,J＝7.4Hz,1H),6.66(d,J＝3.2Hz,1H),4.53(m,1H),4.08(t,J＝12.3Hz,1H),3.29(dd,J＝18.1,9.3Hz,1H),2.82(dd,J＝18.4,4.9Hz,1H),2.29–2.20(m,2H),1.88–1.85(m,2H),1.71–1.68(m,3H),1.56(s,9H),1.40–1.29(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ179.13,178.46,176.82,135.11,132.10,126.53,126.29,126.23,124.10,120.57,107.91,51.83,43.76,41.71,36.74,29.09,28.86,28.73,25.84,25.82,25.01ppm.
example 2
N-pivaloyl indole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were each added to a 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver acetate (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 7 hours, the reaction was stopped. Adding water and dichloromethane into the reaction system, separatingThe organic layer was washed three to five times with dichloromethane. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 36.3mg of the product in 48% yield, as shown in the following formula:
example 3
N-pivaloyl indole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were each added to a 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), pivalic acid (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 24 hours, substantially no product was formed, and the reaction was as follows:
example 4
N-pivaloyl indole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were each added to a 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgNTf 2 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 4 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 37.8mg of the product in 50% yield, as shown in the following formula:
example 5
N-pivaloyl indole (0.2 mmol) and N-hop-indole were added to 4mL reaction flask at room temperatureCyclohexylmaleimide (0.6 mmol), [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and HFIP (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 3 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 15.1mg of the product in 20% yield, as shown in the following formula:
example 6
N-pivaloyl-3-methylindole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were each added to a 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 4 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 50.2mg of the product in 64% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.44(d,J＝7.7Hz,1H),7.41(s,1H),7.28(t,J＝7.1Hz,1H),7.04(d,J＝7.4Hz,1H),4.49(m,1H),4.05(t,J＝12.2Hz,1H),3.26(dd,J＝18.2,9.4Hz,1H),2.77(dd,J＝18.4,5.0Hz,1H),2.28(s,3H),2.23–2.17(m,2H),1.86–1.82(m,2H),1.68–1.66(m,3H),1.52(s,9H),1.35–1.26(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ178.72,178.55,176.93,135.62,133.10,126.51,126.46,123.92,123.54,118.45,116.80,51.83,44.00,41.53,36.89,29.09,28.87,28.73,25.86,25.84,25.03,9.66ppm.
example 7
N-pivaloyl-4-methoxyindole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were added to a 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 4 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 47.4mg of the product in 58% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.53(d,J＝3.7Hz,1H),6.96(d,J＝8.3Hz,1H),6.76(d,J＝3.7Hz,1H),6.68(d,J＝8.3Hz,1H),4.44(m,1H),4.07–4.00(m,1H),3.91(s,3H),3.21(dd,J＝18.2,9.4Hz,1H),2.74(dd,J＝18.3,5.1Hz,1H),2.25–2.16(m,2H),1.85–1.82(m,2H),1.67–1.62(m,3H),1.53(s,9H),1.37–1.18(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ179.33,178.81,176.97,152.47,136.17,124.95,124.22,122.21,118.70,104.68,104.16,55.48,51.79,43.26,41.80,36.82,29.08,28.88,28.76,25.87,25.85,25.04ppm.
example 8
N-pivaloyl-5-chloroindole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were added to 4mL reaction flask at room temperature, [ RhCp ] Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 24 hours, the reaction was stopped.Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 49.5mg of the product in 60% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.66(d,J＝3.7Hz,1H),7.48(s,1H),7.00(s,1H),6.57(d,J＝3.7Hz,1H),4.51(m,1H),4.06–4.00(m,1H),3.22(dd,J＝18.2,9.4Hz,1H),2.78(dd,J＝18.3,5.3Hz,1H),2.24–2.13(m,2H),1.85–1.82(m,2H),1.67–1.65(m,3H),1.52(s,9H),1.34–1.25(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ179.02,177.72,176.25,133.82,133.67,133.29,129.49,127.82,127.31,120.09,107.23,51.96,43.31,41.77,36.31,29.04,28.82,28.73,25.82,25.81,24.99ppm.
example 9
N-pivaloyl-5-pivaloyloxy indole (0.2 mmol), N-cyclohexylmaleimide (0.6 mmol) and [ RhCp ] Cl were each introduced into a 4mL reaction flask at room temperature 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 7 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (15% ethyl acetate in petroleum ether) to give 59.3mg of the product in 62% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.67(d,J＝3.7Hz,1H),7.24(d,J＝1.8Hz,1H),6.74(s,1H),6.59(d,J＝3.7Hz,1H),4.57(m,1H),4.02(tt,J＝11.9,3.3Hz,1H),3.19(dd,J＝18.0,9.3Hz,1H),2.81(dd,J＝18.3,5.4Hz,1H),2.20–2.15(m,2H),1.84–1.81(m,2H),1.64(m,3H),1.53(s,9H),1.35(s,9H),1.30–1.25(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ178.91,177.89,177.14,176.44,147.43,132.81,132.75,127.64,126.49,112.97,107.85,51.89,43.57,41.72,39.06,36.13,29.10,28.79,28.72,27.12,25.84,25.01ppm.
example 10
N-pivaloyl-6-fluoroindole (0.2 mmol) and N-cyclohexylmaleimide (0.6 mmol) were added to a 4mL reaction flask at room temperature, respectively, [ RhCp. Times. Cl ] 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 24 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (20% ethyl acetate in petroleum ether) to give 62.6mg of the product in 79% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.61(d,J＝3.7Hz,1H),7.44(dd,J＝8.4,5.5Hz,1H),7.04(dd,J＝10.9,8.7Hz,1H),6.58(d,J＝3.7Hz,1H),4.09–4.01(m,2H),3.51(m,1H),2.84(dd,J＝18.5,6.0Hz,1H),2.26–2.15(m,2H),1.85–1.82(m,2H),1.71–1.64(m,3H),1.52(s,9H),1.35–1.27(m,3H)ppm； 13 C NMR(101MHz,CDCl 3 )δ179.21,178.35,176.75,159.73(d,J＝241.4Hz),136.35(d,J＝3.3Hz),128.13,127.00(d,J＝3.3Hz),121.01(d,J＝11.1Hz),114.70(d,J＝6.6Hz),112.49(d,J＝25.2Hz),107.99,51.90,41.65,40.92,35.99,29.03,28.57,28.49,25.86,25.09ppm； 19 F NMR(565MHz,CDCl 3 )δ-74.51,-117.34ppm
example 11
N-pivaloyl-3-methylindole (0.2 mmol), N- (1, 3, 5-trichloro) phenylmaleimide (0.6 mmol) and [ RhCp. Times. Cl were each introduced into a 4mL reaction flask at room temperature 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 3 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 60mg of the product in 61% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.50–7.48(m,3H),7.44(s,1H),7.36–7.31(m,2H),4.98(dd,J＝9.5,5.4Hz,1H),3.68(dd,J＝18.8,9.6Hz,1H),3.16(dd,J＝18.8,5.4Hz,1H),2.29(s,3H),1.55(s,9H)ppm； 13 C NMR(101MHz,CDCl 3 )δ178.98,175.70,173.89,136.47,135.66,135.17,135.13,133.19,128.80,128.75,127.47,125.59,124.08,123.71,123.65,118.84,116.82,44.63,41.64,37.63,29.14,9.67ppm.
example 12
N-pivaloyl-5-chloroindole (0.2 mmol) and N-benzylmaleimide (0.6 mmol) were added to 4mL reaction flask at room temperature, respectively, [ RhCp. Times. Cl ] 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 4 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. Combining all organic layers with anhydrous sulfuric acidSodium was dried, concentrated, and separated by column chromatography (10% ethyl acetate in petroleum ether) to give 48.2mg of the product in 57% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.67(d,J＝3.8Hz,1H),7.48(d,J＝1.8Hz,1H),7.43–7.41(m,2H),7.36–7.28(m,3H),6.94(s,1H),6.57(d,J＝3.8Hz,1H),4.78–4.58(m,2H),4.58(m,1H),3.31(dd,J＝18.3,9.3Hz,1H),2.90(dd,J＝18.3,4.8Hz,1H),1.50(s,9H)ppm； 13 C NMR(101MHz,CDCl 3 )δ179.00,177.36,175.82,135.71,133.53,133.34,129.52,128.82,128.68,128.00,127.86,126.90,126.82,120.21,107.30,43.98,42.60,41.71,36.58,29.00ppm
example 13
N-pivaloyl-6-methoxyindole (0.2 mmol), N-ethylmaleimide (0.6 mmol) and [ RhCp. Times. Cl were each added to a 4mL reaction flask at room temperature 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 1 hour, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (25% ethyl acetate in petroleum ether) to give 53.5mg of the product in 75% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(600MHz,)δ7.51(d,J＝3.8Hz,1H),7.45(d,J＝8.5Hz,1H),6.93(d,J＝8.5Hz,1H),6.53(d,J＝3.8Hz,1H),3.90(dd,J＝9.2,5.8Hz,1H),3.75(s,3H),3.66–3.62(m,2H),3.52(dd,J＝18.4,9.4Hz,1H),2.88(dd,J＝18.4,5.7Hz,1H),1.51(s,9H),1.25(t,J＝7.2Hz,3H)ppm； 13 C NMR(151MHz,)δ179.53,179.50,177.45,155.40,137.53,126.08,126.01,120.64,114.90,108.84,108.04,56.03,42.11,41.63,35.45,33.62,29.09,13.14ppm.
example 14
N-pivaloyl primary color alcohol (0.2 mmol), N-cyclohexylmaleimide (0.6 mmol) and [ RhCp ] Cl were each added to a 4mL reaction flask at room temperature 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 4 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (15% ethyl acetate in petroleum ether) to give 59mg of the product in 58% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.52(d,J＝7.7Hz,1H),7.48(s,1H),7.28(t,J＝8.2Hz,1H),7.05(d,J＝7.5Hz,1H),4.47(dd,J＝8.9,4.9Hz,1H),4.37(t,J＝6.8Hz,2H),4.04(tt,J＝12.3,3.5Hz,1H),3.26(dd,J＝18.3,9.4Hz,1H),3.03(t,J＝6.8Hz,2H),2.78(dd,J＝18.4,5.1Hz,1H),2.25–2.16(m,2H),1.85–1.82(m,2H),1.68–1.65(m,3H),1.52(s,9H),1.37–1.24(m,3H),1.18(s,9H)ppm； 13 C NMR(101MHz,CDCl 3 )δ178.90,178.54,178.50,176.88,135.60,132.07,126.63,126.58,124.06,123.91,118.44,117.25,63.17,51.86,43.92,41.62,38.70,36.80,29.08,28.87,28.73,27.16,25.85,25.83,25.02,24.50ppm.
example 15
N-pivaloyl-primary amine (0.2 mmol) and N-cyclohexylmaleimide (0.6) were added to 4mL reaction flask at room temperaturemmol)、[RhCp*Cl 2 ] 2 (0.01mmol)、AgSbF 6 (0.04 mmol), silver oxide (0.4 mmol), and TFE (2.0 mL). Heating to 80 deg.C and stirring. The reaction was monitored by TLC. After 4 hours, the reaction was stopped. Water and methylene chloride were added to the reaction system, the organic layer was separated, and the aqueous layer was washed three to five times with methylene chloride. All organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography (35% ethyl acetate in petroleum ether) to give 60.9mg of the product in 60% yield, as shown in the following formula:
nuclear magnetic resonance analysis was performed on the product prepared in this example:
1 H NMR(400MHz,CDCl 3 )δ7.50(d,J＝7.6Hz,1H),7.47(s,1H),7.27(t,J＝7.6Hz,1H),7.03(d,J＝7.4Hz,1H),5.80(brs,1H),4.44(dd,J＝8.7,4.9Hz,1H),4.07–4.00(m,1H),3.64–3.53(m,2H),3.27(dd,J＝18.3,9.4Hz,1H),2.91(t,J＝6.7Hz,2H),2.77(dd,J＝18.4,5.1Hz,1H),2.25–2.15(m,2H),1.85–1.82(m,2H),1.67–1.64(m,3H),1.51(s,9H),1.34–1.25(m,3H),1.16(s,9H)ppm； 13 C NMR(101MHz,CDCl 3 )δ178.98,178.59,178.54,176.87,135.80,132.04,126.78,126.72,124.08,123.88,118.46,118.17,51.87,43.90,41.62,38.87,38.64,36.83,29.06,28.87,28.73,27.54,25.84,25.82,25.23,25.01ppm。
Claims (6)
1. a process for preparing 7-succinimidyl indole compounds features that in solvent, [ RhCp ] Cl 2 ] 2 As catalyst, agSbF 6 Reacting with silver oxide as an additive, and carrying out post-treatment after the reaction is finished to obtain the 7-succinimidyl indole compound;
the structure of the 7-succinimidyl indole compound is shown in any one of formulas (I) to (VI):
in the formula (I), R 1 Is hydrogen, C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, C 1 ～C 4 Alkanoyloxy or halogen;
the structure of the indole compound is shown in any one of formulas (VII) to (IX):
in the formula (VII), R 1 Is hydrogen, C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, acyloxy or halogen;
the maleimide compound has a structure represented by any one of chemical formulas (X) to (XI):
in the formula (X), R 2 Is cyclohexyl, C 1 ～C 4 Alkyl or benzyl;
the reaction temperature is 75-85 ℃;
the solvent is trifluoroethanol.
2. The process for preparing 7-succinimidyl indoles according to claim 1, wherein R 1 Is hydrogen, methyl, methoxy, pivaloyloxy, fluoro or chloro.
3. The process for preparing 7-succinimidyl indoles according to claim 1, wherein R 2 Is cyclohexyl, ethyl or benzyl.
4. The process for producing a 7-succinimidyl indole compound according to claim 1, wherein the reaction time is 1 to 24 hours.
5. The method for preparing 7-succinimidyl indole compounds according to claim 1, wherein the molar ratio of indole compounds to maleimide compounds is 1:2.5 to 3.5; the indole compound and the catalyst [ RhCp ] Cl 2 ] 2 Additive AgSbF 6 The mol ratio of the silver oxide is 1:0.045-0.055:0.15-0.25:1.5-2.5.
6. The method for preparing 7-succinimidyl indole compounds according to claim 1, wherein the post-treatment process is as follows: adding water and dichloromethane into the reaction system, separating an organic layer, washing an aqueous layer three to five times by using the dichloromethane, combining all the organic layers, drying by using anhydrous sodium sulfate, concentrating, and separating by column chromatography to obtain the 7-succinimidyl indole.
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