Practical and Scalable Synthetic Method for Preparation of Dolutegravir Sodium: Improvement of a Synthetic Route for Large-Scale Synthesis

被引：16

作者：

Aoyama, Yasunori ^{[1
]}

Hakogi, Toshikazu ^{[2
]}

Fukui, Yuki ^{[1
]}

Yamada, Daisuke ^{[1
]}

Ooyama, Takao ^{[3
]}

Nishino, Yutaka ^{[2
]}

Shinomoto, Shoji ^{[1
]}

Nagai, Masahiko ^{[3
]}

Miyake, Naoki ^{[2
]}

Taoda, Yoshiyuki ^{[3
]}

Yoshida, Hiroshi ^{[3
]}

Yasukata, Tatsuro ^{[1
]}

机构：

[1] Shionogi & Co Ltd, CMC R&D Div, API R&D Lab, 1-3,Kuise Terajima 2 Chome, Amagasaki, Hyogo 6600813, Japan

[2] Shionogi & Co Ltd, Mfg Div, Prod Technol Dept, 1-3,Kuise Terajima 2 Chome, Amagasaki, Hyogo 6600813, Japan

[3] Shionogi & Co Ltd, Shionogi Pharmaceut Res Ctr, 1-1,Futaba Cho 3 Chome, Toyonaka, Osaka 5610825, Japan

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 04期

关键词：

dolutegravir sodium; oxidation of maltol methyl group; intramolecular aminolysis; palladium-catalyzed amidation;

D O I：

10.1021/acs.oprd.8b00409

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A practical and scalable synthetic method to obtain dolutegravir sodium (1) was established starting from the readily accessible material maltol (2). This synthetic method includes a scalable oxidation process of maltol and palladium-catalyzed amidation for introduction of an amide moiety, leading to a practical manufacturing method in short synthetic steps. The synthetic method demonstrated herein enables multikilogram scale manufacturing of 1 of high purity.

引用

页码：558 / 564

页数：7

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