Process Development of CP-481715, a Novel CCR1 Antagonist

Abstract

Process development for the synthesis of 2-quinoxalinecarboxamide, N-[(1S,2S,4R)-4-(aminocarbonyl)-1-[(3-fluorophenyl)methyl]-2,7-dihydroxy-7-methyloctyl] is described. An optimized and streamlined process starting from lactone 2 was developed: Lactone 2 was alkylated diastereoselectively with prenyl bromide, followed by deprotection of the N-Boc group and concomitant hydration of the olefin. Aminolysis of the lactone in methanolic ammonia afforded the titled compound.