关键词: 达比加群酯, 非肽类凝血酶抑制剂, 合成

Abstract: 4-Methylamino-3-nitrobenzoic acid(3) was prepared from 3-nitro-4-chlorobenzoic acid by methylamination. 3-[(Pyridin-2-yl)amino]propinoic acid ethyl ester(5) was prepared from 2-aminopyridine and ethyl acrylate by Michael addition. Dabigatran etexilate was synthesized from compounds 3 and 5 via condensation, catalytic hydrogenation, acylation with N-(4-cyanophenyl)glycine(9), cyclization, Pinner reaction, followed by reaction with n-hexyl chlorofomate. The overall yield is about 40% and the structure of the product was determined by IR, 1H NMR and MS.

Key words: dabigatran etexilate, non-peptide thrombin inhibitors, synthesis