噁拉戈利钠合成新工艺研究

New Synthetic Process of Elagolix Sodium

噁拉戈利钠是一种促性腺激素释放激素(GnRH)受体拮抗剂,用于治疗女性中度至重度子宫内膜异位症疼痛。以3-[(2R)-2-氨基-2-苯基乙基]-5-(2-氟-3-甲氧基苯基)-1-[[2-氟-6-(三氟甲基)苯基]甲基]-6-甲基-2,4(1H,3H)-嘧啶二酮水杨酸盐为原料,经酰化、烷基化、还原、水解4步反应合成了噁拉戈利钠,总收率达72%,产品结构经核磁共振氢谱1H NMR和高分辨质谱确证。该工艺原料易得,操作简便,收率较高,适合工业化生产。

Elagolix sodium is a gonadotropin-releasing hormone(GnRH)receptor antagonist for the treatment of moderate to severe endometriosis pain in women.3-[(2R)-2-amino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[[2-fluoro-6-(trifluoromethyl base)phenyl]methyl]-6-methyl-2,4(1H,3H)-pyrimidinedione salicylate was used as raw material to synthesize sodium elagolix through acylation,alkylation,reduction and hydrolysis in 4 steps.The total yield was 72%,and the product structure was confirmed by 1H NMR and high-resolution mass spectrometry.The raw material of the process is easy to obtain,the operation is simple and the yield is high,and it is suitable for industrial production.