title: Development of a two-step route to 3-PBC and βCCt, two agents active against alcohol self-administration in rodent and primate models.
abstract: To gain access to 3-propoxy-β-carboline hydrochloride (3-PBC·HCl) (1·HCl) and β-carboline-3-carboxylate-tert-butyl ester (βCCt) (2), potential clinical agents active against alcohol self-administration, a two-step route was developed. This process involves a palladium-catalyzed Buchwald-Hartwig coupling and an intramolecular Heck reaction. This two-step route provides rapid access to multigram quantities of 3-PBC (1) and βCCt (2), as well as analogues for studies of alcohol self-administration. The overall yield of 3-PBC (1) was improved from 8% to 50% by this route.
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
authors.forename: Ojas A
authors.initials: OA
authors.lastname: Namjoshi
authors.forename: Angelica
authors.initials: A
authors.lastname: Gryboski
authors.forename: German O
authors.initials: GO
authors.lastname: Fonseca
authors.forename: Michael L
authors.initials: ML
authors.lastname: Van Linn
authors.forename: Zhi-jian
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Deschamps
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
mesh_terms: D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002384:Catalysis; D004195:Disease Models, Animal; D015195:Drug Design; D010165:Palladium / Q000737:chemistry; D011323:Primates; D051381:Rats; D012646:Self Administration
chemical_list: C454686:3-propoxy-beta-carboline; D002243:Carbolines; D010165:Palladium; C043232:tert-butyl beta-carboline-3-carboxylate