- A Three-Step Synthesis of Acotiamide for the Treatment of Patients with Functional Dyspepsia
-
A three-step synthesis of acotiamide is described. The agent is marketed in Japan for treatment of patients with functional dyspepsia. We designed a one-pot method to prepare the key intermediate 5a from 2 via an acyl chloride and amide and then reacted w
- Fu, Kai,Yang, Liu,Wang, Qiu-Fen,Zhan, Fu-Xu,Wang, Bin,Yang, Qian,Ma, Zhi-Jia,Zheng, Geng-Xiu
-
-
Read Online
- Preparation method of acotiamide hydrochloride impurity
-
The invention discloses a preparation method of an acotiamide hydrochloride impurity. The method comprises the following steps: carrying out acylating chlorination on a raw material 2,4,5-trimethoxybenzoic acid to obtain 2,4,5-trimethoxybenzoyl chloride, and carrying out an amidation reaction on the 2,4,5-trimethoxybenzoyl chloride and 2-amino-4-ethoxycarbonyl-1,3-thiazole to obtain 2-amino-4-ethoxycarbonyl-1,3-thiazole (intermediate 1); hydrolyzing the intermediate 1 with sodium hydroxide to obtain 2-[N-(2,4,5-trimethoxybenzoyl)amino]-4-carboxyl-1,3-thiazole (intermediate 2); and performing an acylating chlorination reaction on the intermediate 2 to obtain an acyl chloride group, performing an amidation reaction on the acyl chloride group and N,N-diisopropylethylenediamine to obtain N-[2-(diisopropylamino)ethyl]-2-[(2,4,5-trimethoxybenzoyl)amino]-4-thiazole formamide (acotiamide), and performing a salt forming reaction on the acotiamide to obtain acotiamide hydrochloride. The preparation method of the acotiamide hydrochloride impurity has the advantages of mild reaction conditions, simple operation, low cost and high yield, and is suitable for industrial production.
- -
-
Paragraph 0020-0021
(2020/08/02)
-
