239463-72-0Relevant articles and documents
5-substituted indoline derivative or salt thereof, preparation method and application of 5-substituted indoline derivative or salt thereof, and preparation method of silodosin
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, (2022/04/06)
The invention relates to the technical field of medicines, in particular to a 5-substituted indoline derivative or a salt thereof, a preparation method and application of the 5-substituted indoline derivative or the salt thereof, and a preparation method of silodosin. Silodosin can be prepared by taking the 5-substituted indoline derivative provided by the invention as an intermediate through first N-alkylation, bromination, cyano substitution, deprotection, second N-alkylation and hydrolysis. The reaction route is short, and the total yield of the silodosin is high. The 5-substituted indoline derivative salt provided by the invention has good stability. According to the method, phthalic anhydride or substituted phthalic anhydride and D-alanine are taken as starting materials, the 5-substituted indoline derivative can be obtained through condensation, acylating chlorination, Friedel-Crafts reaction, reduction and hydrolysis, the reaction route is short, chiral construction does not need resolution, the atom utilization rate is high, the total yield is larger than 57.5%, and the yield is high; and the raw materials are cheap and easily available, and the production cost is low.
Preparation method of silodosin intermediate
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Paragraph 0102; 0112; 0119; 0122; 0129; 0141; 0148, (2019/04/17)
The invention discloses a preparation method of a silodosin intermediate. The preparation method includes: allowing 5-bromoindoline solution and triethylamine to be in alkylation reaction to obtain asubstance A; allowing a solution of the substance A, ethyl acetoacetate, catalyst and acid-binding agent to be in substitution reaction to obtain a substance B; allowing a solution of the substance Band Lewis acid to be in decarboxylic reaction to obtain a substance C; allowing a solution of the substance C, R-tert butyl sulfonamide, catalyst and reducer to be in amination reaction to obtain a substance D; allowing a solution of the substance D and N-bromosuccinimide solution to be in bromination reaction to obtain a substance E; allowing a solution of the substance E and cuprous cyanide to be in cyanation reaction to obtain a substance F; allowing a solution of the substance F and acid to be in acidolysis reaction to obtain a substance G; preparing the substance G into tartrate to obtainthe silodosin intermediate. The preparation method is simple, high in yield, low in energy consumption and environment-friendly; the silodosin intermediate prepared by the method is high in quality and suitable for large-scale industrial production.
Improved synthetic method of (R)-1-aryl-2-propylamine
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Paragraph 0026; 0028; 0030; 0032; 0034; 0039; 0040; 0041, (2018/07/30)
The invention provides an improved synthetic method of (R)-1-aryl-2-propylamine. The improved synthetic method comprises the following steps of: adopting 1-arylacetone as a raw material, adding (R)-1-phenylethylamine, carrying out reductive amination reaction with hydrogen under a common action of a Lewis acid additive and a transitional metal hydrogenation catalyst; carrying out Pd/C catalytic hydrogenation on an obtained intermediate to remove phenethyl on nitrogen and thus obtaining (R)-1-aryl-2-propylamine. The improved synthetic method provided by the invention has the beneficial effectsthat the operation is simple, the adopted Lewis acid additive is low in cost and easy in obtaining, the yield and the enantioselectivity of a product are high, and the application value for industrialsynthesis of (R)-1-aryl-2-propylamine is very high.