Practical syntheses of a CXCR3 antagonist.

Johann Chan, Brenda J Burke, Kyle Baucom, Karl Hansen, Matthew M Bio, Evan DiVirgilio, Margaret Faul, Jerry Murry

Index: J. Org. Chem. 76 , 1767-1774, (2011)

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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.