6,7-二甲氧乙氧基喹唑啉-4-酮合成新工艺的研究

Study on the Synthesis of 6,7-Dimethoxyethoxyquinazoline-4-One

盐酸埃罗替尼是应用于临床的口服表皮生长因子受体(EGFR)抑制剂,其中6,7-二甲氧乙氧基喹唑啉-4-酮是盐酸埃罗替尼合成的关键中间体。传统的工艺中,该中间体合成条件苛刻,收率较低。本文以2-氨基-4,5-二(2-甲氧基乙氧基)苯甲酸为原料,两步法合成6,7-二甲氧乙氧基喹唑啉-4-酮,总收率达99.2%,产品结构经1HNMR确证。该工艺原料价廉易得、操作简便、收率较高,适合工业化生产。

Erlotinib hydrochloride is the EGFR inhibitor to be used in clinic. 6,7-dimethoxyethoxyquinazoline-4-one is the key intermediate in the synthesis of erlotinib hydrochloride. In the traditional process, the synthesis conditions of the intermediate are harsh and the yield is low. Using 2-amino-4,5-bis(2-methoxyethoxy) benzoic acid as raw material, 6,7-dimethoxyethoxyquinazoline-4-one was synthesized by ultrasonic method with a total yield of 99.2%. The product structure was confirmed by 1 HNMR. The raw material of the process is cheap and easy to obtain, the operation is simple, the yield rate is high, and it is suitable for industrial production.