title: Practical syntheses of a CXCR3 antagonist.
abstract: Two new, reliable syntheses of a pyrido[2,3-d]-pyrimidine inhibitor of the CXCR3 receptor are described. A nine-step synthesis of the CXCR3 inhibitor (1) from 2-aminonicotinic acid was demonstrated on a multikilogram scale and incorporates a classic resolution to deliver the enantioenriched active pharmaceutical ingredient (API). A second synthesis of the CXCR3 inhibitor starts from (+)-(D)-Boc alanine and 2-chloronicotinic acid and utilizes a Goldberg coupling. This second synthesis, performed on a gram scale, intersects the former route at a common intermediate thereby completing a formal synthesis of the enantioenriched API in higher overall yield without the need for a resolution.
authors.affiliation: Chemistry Process Research and Development, Amgen, Inc., Thousand Oaks, California 91320, USA. johannc@amgen.com
authors.forename: Johann
authors.initials: J
authors.lastname: Chan
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Burke
authors.forename: Kyle
authors.initials: K
authors.lastname: Baucom
authors.forename: Karl
authors.initials: K
authors.lastname: Hansen
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Bio
authors.forename: Evan
authors.initials: E
authors.lastname: DiVirgilio
authors.forename: Margaret
authors.initials: M
authors.lastname: Faul
authors.forename: Jerry
authors.initials: J
authors.lastname: Murry
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000409:Alanine / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013644:Tartrates / Q000737:chemistry
chemical_list: D000081:Acetamides; D000447:Aldehydes; D000588:Amines; D006845:Hydrocarbons, Fluorinated; D011743:Pyrimidines; D054367:Receptors, CXCR3; D013644:Tartrates; D000409:Alanine; C029768:tartaric acid