Method for preparing betrixaban intermediate

• Main Authors: SUN DEXIN, ZHANG GUIMIN, BAI WENQIN
• Format: Patent
• Language: Chinese; English
• Published: 09.03.2018
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention provides a method for preparing a betrixaban intermediate. The method comprises the following step of using 5-methoxyl-2-nitrobenzoic acid and 2-amino-5-chloropyridine as initiating rawmaterials, so as to prepare N-(5-chloro-2-pyridyl)-5-methoxyl-2-nitrobenzoic acid. The method has the advantages that the 5-methoxyl-2-nitrobenzoic acid is activated by jointly applying EDC (carbodiimide) and N-hydroxysuccinimide, and is reacted with the 2-amino-5-chloropyridine to obtain the intermediate; the reagents with larger hazard to human bodies and environments, such as phosphorus oxychloride, oxalyl chloride and pyridine, are not used; the reaction conditions, product quality, product cost and the like are improved; especially, the operation is simple, the pollution is little, and the method is suitable for industrialized production. 本发明提供了种制备贝曲西班中间体的方法，以5-甲氧基-2-硝基苯甲酸和2-氨基-5-氯吡啶为起始原料制得N-(5-氯-2-吡啶基)-5-甲氧基-2-硝基苯甲酰胺，该方法中选用EDC和NHS联合应用对5-甲氧基-2-硝基苯甲酸进行活化，在与2-氨基-5-氯吡啶反应得中间体；该制备方法弃用三氯氧磷、草酰氯和吡啶等对人体和环境的危害比较大试剂。反应条