A kind of preparation method of n,n-dimethylacetamide

Abstract

The invention provides a kind of preparation method of N,N-dimethylacetamide, comprising the following steps: 1) reacting pentamidine hydrochloride and dimethyl acetylsuccinate under the effect of organic amine to obtain 2-(2 -n-butyl-4-hydroxyl-6-methylpyrimidin-5-yl)-methyl acetate, the pKa of the organic amine is 8 to 11.5; 2) the 2-(2-n-butyl-4 ‑Hydroxy‑6‑methylpyrimidin‑5‑yl)‑methyl acetate reacts with dimethylamine to give 2‑(2‑n-butyl‑4‑hydroxy‑6‑methylpyrimidin‑5‑yl)‑N, N‑Dimethylacetamide. The preparation method provided by the invention has the advantages of simple reaction and post-treatment process, high atom economy and low cost.

Description

A kind of preparation method of N,N-dimethylacetamide technical field The invention belongs to the field of pharmaceutical synthesis, relate to a kind of preparation method of N,N-dimethylacetamide, relate in particular to a A preparation method of 2-(2-n-butyl-4-hydroxy-6-methylpyrimidin-5-yl)-N,N-dimethylacetamide. Background technique Fimasartan (Fimasartan) is developed by Korea Baoning Pharmaceutical Co., Ltd., which is a novel non-peptide blood vessel. Tensin II receptor antagonist, with selective blocking effect of AT1 receptor. Expressed rapid and Effective antihypertensive effect, very safe and well tolerated, better than other similar drugs. Fimasartan in 2011 It was first listed in South Korea in 2013, and in the United States, Australia and Russia in 2013. The structural formula of Fimasartan is as follows: [0004] Baoning Pharmaceutical Co., Ltd. discloses a kind of preparation of preparing Fimasartan in Korean Patent No. 10-521980 Method, this ...

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Problems solved by technology

[0009] As can be seen from the above reaction process, the compound 2-(2-n-butyl-4-hydroxyl-6-methylpyrimidin-5-yl)-N,N-dimethylacetamide of formula 1 is Fimasartan An important intermediate in the preparation process, but the above method needs to use a condensing agent to activate the carboxyl group in the compound of formula 6 in the preparation of the compound of formula 1. The condensing agent is relatively expensive and will produce by-product urea, thus causing the reaction and post-treatment process More complex, poor atom economy, relatively high reaction cost

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