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研究DPP-Ⅳ抑制剂Dutogliptin L-酒石酸盐的合成。以四氢吡咯为原料,经Boc保护、硼酸化、(+)-蒎烷二醇保护、脱Boc、结晶拆分得(2R)-(1S,2S,3R,5S)-蒎烷二醇-四氢吡咯-硼酸酯盐酸盐,再经氯乙酰氯酰化、亲电取代、脱Boc、脱(+)-蒎烷二醇,最后与L-酒石酸成盐得Dutogliptin的L-酒石酸盐。以四氢吡咯为起始原料,通过8步反应合成得到Du-togliptin L-酒石酸盐,其结构经核磁和质谱确证。该法改进了中间体(2R)-1-{2-[(3R)-吡咯烷-3-基氨基]-乙酰基}-(1S,2S,3R,5S)-蒎烷二醇-四氢吡咯-硼酸酯盐酸盐的合成工艺,所用的起始原料和相关试剂价廉易得,整个路线反应条件相对温和、操作简便。
To study the synthesis of DPP-IV inhibitor Dutogliptin L-tartrate. (2R) - (1S, 2S, 3R, 5S) -Pinanediol-diol was obtained by using Bipyrrole as starting material and Boc protection, borylation and (+ Tetrahydropyrrole - boronate ester hydrochloride, and then by chloroacetyl chloride acylation, electrophilic substitution, off Boc, (+) - pinane diol, and finally salt with L-tartaric Dutogliptin L-tartrate . Using tetrahydropyrrole as the starting material, Du-togliptin L-tartrate was synthesized by 8 steps and its structure was confirmed by NMR and MS. This method improves the synthesis of the intermediate (2R) -1- {2 - [(3R) -pyrrolidin-3- ylamino] -acetyl} - (1S, 2S, 3R, 5S) -Pinanediol- Pyrrole - boronate ester hydrochloride synthesis process, the starting materials used and related reagents cheap, the reaction route is relatively mild, easy to operate.