Large Scale Synthesis of an Ampakine-type Active Pharmaceutical Ingredient Based on a Telescoped Regioselective Double Amidation Reaction

被引：4

作者：

Hardouin, Christophe ^{[1
]}

Pin, Frederic ^{[1
]}

Giffard, Jean-Francois ^{[1
]}

Hervouet, Yvon ^{[1
]}

Hublet, Julie ^{[1
]}

Janvier, Solenn ^{[1
]}

Penloup, Christine ^{[1
]}

Picard, Julien ^{[1
]}

Pinault, Nathalie ^{[1
]}

Schiavi, Bruno ^{[1
]}

Zhang, Peng ^{[2
]}

Zhao, Weiwei ^{[2
]}

Zhu, Xueyan ^{[2
]}

机构：

[1] Oril Ind, Ind Res Ctr, 13 Rue Desgenetais, F-76210 Bolbec, France

[2] China State Inst Pharmaceut Ind, Shanghai Inst Pharmaceut Indus, 285 Gebaini Rd, Shanghai 201203, Peoples R China

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 09期

关键词：

regioselective CDI-mediated amidation; protecting-group-free synthesis; telescoped process; AMPA receptors; POSITIVE ALLOSTERIC MODULATOR; LONG-TERM POTENTIATION; RECEPTOR MODULATORS; S; 47445; COMPLEX;

D O I：

10.1021/acs.oprd.9b00241

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

This work describes the process development and manufacture of an ampakine-type active pharmaceutical ingredient in clinical trials. A regioselective CDI-mediated amidation process was optimized for the subsequent couplings of two distinctive amines with a terephthalic acid substrate. Choice of the synthetic route, key scale-up issues, safety calorimetry, and optimization of all steps for multikilogram production are discussed.

引用

页码：1932 / 1947

页数：16

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