种(R)-3-氨基-1,2,3,4-四氢咔唑的合成方法

• Format: Patent
• Language: Chinese
• Published: 28.09.2018
• Subjects: CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

本发明公开了种雷马曲班中间体(R)-3-氨基-1,2,3,4-四氢咔唑的合成方法。本发明的合成方法为：1,4-环己二酮单乙二醇缩酮和苯肼经过醛酮胺缩合，再关环得到3,3_乙烯基二氧-1,2,4,9-四氢咔唑-3-酮，然后再脱去保护基团得到1,2,4,9-四氢咔唑-3-酮；1,2,4,9-四氢咔唑-3-酮再与O-烷基羟胺盐酸盐反应得到肟醚，肟醚经过低温手性选择性还原直接得到(R)-3-氨基-1,2,3,4-四氢咔唑。本文发明提供了药物雷马曲班的重要中间体(R)-3-氨基-1,2,3,4-四氢咔唑的种新合成路线，合成方法简单方便，操作条件温和，反应收率高，可进行放大反应，应用于工业化生产。 The invention discloses a synthesis method for a Ramatroban intermediate (R)-3-amino-1,2,3,4-tetrahydrocarbazole.The synthesis method includes the steps that 1,4-cyclohexanedione monoethylene acetal and phenylhydrazine are subjected to aldehyde ketone amine condensation, then cyclization is conducted to obtain 3,3-vinyl dioxo-1,2,4,9-tetrahydrocarbazole-3-ketone, then protecting groups are removed to obtain 1,2,4,9-tetrahydrocarbazole-3-ketone, 1,2,4,9-tetrahydrocarbazole-3-ketone and O-hydroxylamine hydrochloride react to obtain oxime ether, and oxime ether is subjected to low-temperature chiral selective reduction to directly obtain (R)-3-amino-1,2,3,4-tetrahydrocarbazole.A new synthesis route of the important inter