Convenient efficient synthesis of TAK-779, a nonpeptide CCR5 antagonist: development of preparation of various ammonium salts using trialkylphosphite and N-halogenosuccinimide

A convenient and efficient synthesis of TAK-779 (1a), a nonpeptide CCR5 antagonist, has been achieved. The new methylation of tertiary amine (2) using trimethyl phosphite and N-chlorosuccinimide, followed by the addition of HCl led to ammonium chloride (1a) in 89% isolated yield without requiring a chromatographic method. By this preparation, ammonium methanesulfonate (1e) could be obtained in 75% isolated yield.