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| Study on synthesis of acoteine trihydrate hydrochloride |
| Liu Xiaolian, Ma Ningning, Yang Cangjun, Han Xiao, Xu Yawei, Dai guoai |
| Hebei Jiheng Pharmaceutical Corporation Ltd., Hengshui 053400, China |
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Abstract A synthesis method was provided that acogtinamide hydrochloride produced by acid chlorination, substitution, demethylation, ester amination, and hydrochlorination with 2,4,5-trimethoxybenzoic acid as the starting material. The best process conditions are as follows: n (2, 4,5-Tritrimethoxybenzoic acid) (AKTA-1)∶ n (dichlorosulfoxide) =1∶1.5, 80 ℃, Reaction for 4 h, Synthetic AKTA-2; n(AKTA-2)∶ n(2-aminothiazole-4-ethyl formate) =1.5∶1, 40 ℃, AKTA-4 was obtained in the reaction at 4 h; For n (AKTA-4)∶ n(pyridine hydrochloride)∶ n(pyridine) =1∶10∶2, 165 ℃, AKTA-5 was obtained at 16 h of the reaction; n(AKTA-5)∶n(N, N-diisopropyl ethylenediamine) =1∶10, 120 ℃, Crude acoutinamide for 4 h of reaction; Finally with hydrochloride. The whole process yield was 20% as tested by HPLC. The purity of the finished product was up to 99.81%.
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