title: Process research and development for a tetrazole-based growth hormone secretagogue (GHS) pharmaceutical development candidate.
abstract: 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.
authors.affiliation: Process Research and Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey 08903, USA. akin.davulcu@bms.com
authors.forename: Akin H
authors.initials: AH
authors.lastname: Davulcu
authors.forename: Douglas D
authors.initials: DD
authors.lastname: McLeod
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Kishta
authors.initials: K
authors.lastname: Katipally
authors.forename: Adam
authors.initials: A
authors.lastname: Littke
authors.forename: Wendel
authors.initials: W
authors.lastname: Doubleday
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Xu
authors.forename: Cary W
authors.initials: CW
authors.lastname: McConlogue
authors.forename: Chiajen J
authors.initials: CJ
authors.lastname: Lai
authors.forename: Margaret
authors.initials: M
authors.lastname: Gleeson
authors.forename: Mark
authors.initials: M
authors.lastname: Schwinden
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Parsons
mesh_terms: D002219:Carbamates; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D054440:Receptors, Ghrelin / Q000819:agonists*; D012107:Research Design; D013777:Tetrazoles
chemical_list: 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