普拉格雷的合成

Synthesis of prasugrel

目的合成普拉格雷。方法邻氟苯乙酸钠和格氏试剂反应生成伊万诺夫试剂,然后和环丙基甲酸甲酯反应得到环丙基-2-氟苄基酮,经无溶剂溴化反应得到α-环丙羰基-2-氟苄基溴,再与5,6,7,7a-四氢噻吩并[3,2-c]吡啶-2(4H)-酮缩合、乙酰化得到普拉格雷。结果该方法普拉格雷的总收率为35%。结论此工艺收率高、成本低、易于工业化。

Objective To synthesize prasugrel. Methods Ivanov reagent was synthesized from sodium 2 - fluorophe-nylacetate and grignard reagent, then reacted with methyl cyclopropanecarboxylate to give cyclopropyl 2 - fluorobenzyl ke-tone. Then, under solvent - free conditions 2 - fluoro - α - cyclopropylcarbonyl - benzyl bromine was obtained through the bromination of cyclopropyl 2 - fluorobenzyl ketone, which was subjected to condensation with 5,6,7,7a - tetrahydrothieno [ 3,2 -c] pyridine -2（4H）-one hydrochloride,and acetylation to give prasugrel. Results The total yield of this method was 35%. Conclusion The process was simple and feasible with low cost,and it was suitable for industrial production.