Process research and development for a tetrazole-based growth hormone secretagogue (GHS) pharmaceutical development candidate.
BMS-317180 (1) is a potent, orally active agonist of the human growth hormone secretagogue (GHS) receptor. This manuscript details the process research and development efforts that enabled the synthesis of the phosphate salt of 1 on a multi-kilogram scale. Key considerations in the development of this process focused on safe execution and the requirement for telescoped synthetic transformations (i.e., without isolation of intermediate products) to contend with a lack of suitably crystalline products.
Davulcu
Akin H
AH
Process Research and Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey 08903, USA. akin.davulcu@bms.com
McLeod
Douglas D
DD
Li
Jun
J
Katipally
Kishta
K
Littke
Adam
A
Doubleday
Wendel
W
Xu
Zhongmin
Z
McConlogue
Cary W
CW
Lai
Chiajen J
CJ
Gleeson
Margaret
M
Schwinden
Mark
M
Parsons
Rodney L
RL
D002219:Carbamates; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D054440:Receptors, Ghrelin / Q000819:agonists*; D012107:Research Design; D013777:Tetrazoles
C526808:4-(hydroxybutyl)carbamic acid 2-(5-(1-(2-amino-2-methylpropionylamino)-2-benzyloxyethyl)tetrazol-1-yl)ethyl ester; D002219:Carbamates; D054440:Receptors, Ghrelin; D013777:Tetrazoles; C045574:1H-tetrazole