Details

Autor(en) / Beteiligte

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

Titel

Practical synthesis of capromorelin, a growth hormone secretagogue, via a crystallization-induced dynamic resolution

Ist Teil von

• Bioorganic & medicinal chemistry, 2017-02, Vol.25 (3), p.1000-1003

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] 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.