吉非替尼有关物质的合成

Synthesis of the related substances of gefitinib

摘要: 为控制吉非替尼的药品质量，建立吉非替尼原料药的质量标准，从吉非替尼的合成路线入手，分析并合成其中可能存在的4个有关物质:4-(3-氯-4-氟苯基)氨)-7-甲氧基喹唑啉-6-醇( A )、N-(3-氯-4-氟苯基)-6，7-二甲氧基喹唑啉-4-胺( B )、4-(3-氯-4-氟-苯基)氨基)-7-甲氧基喹唑啉-6-基)氧基)丙基)氨基)乙醇( C )和N-(3，4-二氯苯基)-7-甲氧基-6-(3-吗啉代)喹唑啉-4-胺( D )，并经¹H NMR和MS确证结构。

Abstract: To strengthen the quality control over gefitinib and establish its quality criterion, four related substances of gefitinib were identified based on the synthetic route and synthesized, and their structures were confirmed by ¹H NMR and MS. These substances were 4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ol( A ), N-(3-chloro-4-fluorophenyl)-6, 7-dimethoxyquinazolin-4-amine( B ), 4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propylamino)ethanol( C )and N-(3, 4-dichlorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine( D ).