0

Practical Synthesis of Capromorelin, a Growth Hormone Secretagogue, via a Crystallization-Induced Dynamic Resolution

Colin R Rose, Michael P Zawistoski, Bruce A Lefker, F Michael Mangano, Ann S Wright, Philip A Carpino

Bioorg Med Chem. 2017 Feb 1;25(3):1000-1003.

PMID: 28012686

Abstract:

A practical synthesis of capromorelin (1), a growth hormone secretagogue, is described that utilizes as a key step a crystallization-induced dynamic resolution (CIDR) of (±)-3a-benzyl-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-3(3aH)-one [(±)-2] by L-tartaric acid salt formation, yielding (R)-2.L-tartaric acid in high chemical yield (>85%) and with diastereomeric excess (de) of ∼98%. Treatment of (R)-2.L-tartaric acid with ammonium hydroxide provided (R)-2 without loss of chiral purity. In situ generated (R)-2 was coupled with (R)-3-(benzyloxy)-2-(2-(tert-butoxycarbonyl)-2-methylpropanamido)propanoic acid [(R)-3] to give predominantly a single diastereomer of N-Boc-protected capromorelin [(1R,3aR)-4]. This process was used to prepare bulk quantities of capromorelin from (±)-2 to support preclinical toxicology studies.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP870718073 3-Benzyloxy-2,6-difluorophenylboronic acid 3-Benzyloxy-2,6-difluorophenylboronic acid 870718-07-3 Price
qrcode

We use cookies to understand how you use our site and to improve the overall user experience. This includes personalizing content and advertising. Read our Privacy Policy

Accept Cookies
x