抗痴呆药物CPI-1189的合成工艺改进

Improved synthesis of anti-dementia drug CPI-1189

目的合成抗痴呆药物4-乙酰氨基-N-(叔丁基)苯甲酰胺(CPI-1189)并优化其合成工艺。方法以4-硝基苯甲酸为起始原料,经过酰氯化、酰胺化、催化转移氢化和N-乙酰化4步反应合成目标化合物。结果目标化合物的总收率为67.9%,其化学结构经元素分析、1H-NMR、MS谱确证。结论与文献报道的方法相比较,本工艺以氯化亚砜为氯化剂,降低了成本,并改进了硝基还原反应工艺,缩短了反应时间,使操作条件更为简单、实用。

4-Acetamide-N- （ tert-butyl ） benzamide （ CPI-1189 ） treatment of dementia, associated with AIDS virus（HIV-1 ） infection was synthesized from 4-nitrobenzoic acid via 4-step reactions, including chlorina- tion, amidation, reduction and N-acylation. The 4-nitrobenzoic acid reacted with thionyl chloride to give 4-ni- trobenzoyl chloride, which was condensed with ten-butyl amine to give N-（ tea-butyl）-4-nitrobenzamide （2）. The nitro group of compound 2 was then reduced to amino group [ 4-amino-N- （ten-butyl） benzamide, 3 ] by transfer hydrogenation with hydrazine and 5 % Pd/C. Finally, acylation of amino group compound 3 with acetyl chloride provided the title compound. The overall yield of the target compound was 67.9 %, and its structure was confirmed by elemental analysis, MS, and 1H-NMR. In comparison with the reported proce- dure, the improved process has the advantage of low cost, simple operation, short reaction time and aptness for industrial production.