Process Development for the Manufacture of the Antimalarial Amodiaquine Dihydrochloride Dihydrate

被引：0

作者：

Gohain, Mukut ^{[1
]}

Malefo, Modibo S. ^{[1
]}

Kunyane, Phaladi ^{[1
]}

Scholtz, Chantal ^{[1
]}

Baruah, Sangeeta ^{[1
]}

Zitha, Andile ^{[1
]}

van der Klashorst, Gerrit

Malan, Hannes ^{[1
]}

机构：

[1] Chem Proc Technol Pty Ltd, Dept Res & Dev, ZA-0184 City Of Tshwane, Gauteng, South Africa

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2023年 / 28卷 / 01期

关键词：

antimalarial; amodiaquine dihydrochloride dihydrate; 4,7-dichloroquinoline; meta-chloroaniline; process; MALARIA;

D O I：

10.1021/acs.oprd.3c00205

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A robust process for the manufacture of the active pharmaceutical ingredient (API) amodiaquine dihydrochloride dihydrate (ADQ, 3), an important antimalarial, is reported. The process consists of a three-step synthetic route that involves a Mannich reaction, substitution with 4,7-dichloroquinoline (4,7-DCQ, 5), and rehydration. Additionally, a cost-competitive process for the production of 4,7-DCQ (5) is also reported wherein 4,7-DCQ (5) was prepared in four steps from meta-chloroaniline (7). 4-Acetamido-2-(diethylaminomethyl)-phenol (14), 4,7-DCQ (5), and ADQ (3) were obtained in yields of 92, 89, and 90%, respectively. Costing and process mass intensities of 4,7-DCQ and ADQ are also reported.

引用

页码：124 / 131

页数：8