193274-08-7Relevant articles and documents
Practical synthesis of capromorelin, a growth hormone secretagogue, via a crystallization-induced dynamic resolution
Rose, Colin R.,Zawistoski, Michael P.,Lefker, Bruce A.,Mangano, F. Michael,Wright, Ann S.,Carpino, Philip A.
, p. 1000 - 1003 (2017/02/05)
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.
Process for preparing growth hormone secretagogues
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, (2008/06/13)
This invention relates to improved processes for preparing compounds of Formula II, and compounds of Formula III, wherein R1, R2, R3 and Prt are defined as set forth in the specification.