Amlodipine besylate compound and novel preparation method thereof

Abstract

The invention relates to an amlodipine besylate compound and a novel preparation method thereof, wherein the method comprises the following steps that: a moderate amino-protecting reagent of di-tert-butyl dicarbonate is adopted so that the introduction of a Boc protecting group is realized, through the reaction of intermediums of 3-amino-crotonic acid methyl ester and 2-chlorobenzaldehyde, the obtained amlodipine besylate compound is directly carried out BOC protecting group removal reaction with benzene sulfonic acid, and the final product is obtained. Consequently, the invention is dispensed with the special deprotection step, simplifies the reaction steps, is more suitable for industrialized production and has high total reaction yield.

Description

technical field The invention relates to an amlodipine besylate compound and a new preparation method thereof, belonging to the technical field of medicine. Background technique Amlodipine besylate, chemical name: 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro- 6-Methyl-3,5-pyridinedicarboxylate benzenesulfonate, molecular formula: C 20 h 25 N 2 o 5 Cl·C 6 h 6 o 3 S, molecular weight: 567.1, structural formula: Amlodipine besylate is a third-generation dihydropyridine calcium antagonist developed by Pfizer of the United States. It is mainly used for the treatment of hypertension and angina. It was first launched in the UK in 1990, and its sales have increased year by year. The top selling product among ion antagonists. Compared with other similar drugs, this drug has three characteristics: (1) The blood pressure is stable and mild, and the incidence of adverse reactions is lower than that of conventional antagonists such as nifedipine; (2) ...

AI Technical Summary

Problems solved by technology

In order to overcome the low defect of the productive rate that occurs in the production of amlodipine besylate compound of the above-mentioned prior art, a large number of tests have been done, and the protection reagent di-tert-butyl dicarbonate (BOC) that adopts amino gentle protection reagent, through starting raw material tert-butyl Butoxycarbamide ethanol (HO(CH 2 ) 2 NH (t-BOC)) reacts with ethyl 4-chloroacetoacetate to introduce the Boc protecting group, and then reacts the intermediate 3-aminocrotonate methyl ester and 2-chlorobenzaldehyde to obtain amlodipine compound and benzene The direct reaction of sulfonic acid removes the BOC protecting group to obtain the final product

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