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目的设计合成PARP抑制剂veliparib,并对其合成工艺进行优化。方法以(R)-吡咯烷-2-羧酸为起始原料,经过环合、甲基化、开环、N-H保护、水解、酸氨缩合、咪唑合环、脱保护和成盐酸盐等步骤不对称合成目标化合物veliparib。结果设计的合成路线与文献不同,目标化合物veliparib的合成总收率为9.48%,目标化合物和中间体的结构经1H-NMR和GC-MS确证。结论设计了全新的合成路线,该路线具有原料易得、价格低廉、操作简便、安全等优点,避免了使用手性柱分离目标化合物,适合于工业化生产。
Objective To design a synthetic PARP inhibitor veliparib and optimize its synthesis process. Methods (R) - pyrrolidine-2-carboxylic acid as starting material, through cyclization, methylation, ring opening, NH protection, hydrolysis, acid ammonia condensation, imidazole ring, deprotection and into the hydrochloride Step asymmetric synthesis of the target compound veliparib. Results The design route was different from that of the literature. The total yield of the target compound veliparib was 9.48%. The structures of target compounds and intermediates were confirmed by 1H-NMR and GC-MS. Conclusion A new synthesis route has been designed. This route has the advantages of easy availability of raw materials, low cost, easy operation and safety, and avoids the separation of the target compound by chiral column, which is suitable for industrial production.