Synthesis and characterization of impurities of an anticonvulsant drug, Pregabalin

Abstract

During the process development of Pregabalin 1, a known anticonvulsant drug, six potential impurities were identified in the final crude material ranging from 0.01 to 0.15% by LCMS. All six impurities were subsequently synthesized and characterized by IR, MS and NMR spectral data. Four of the six related substances are known as 4-isobutylpyrrolidin-2-one 6, 3-isobutylglutaric acid 2, (R)-(-)-3-carbamoylmethyl-5-methylhexanoic acid 5 and (R)-(-)-3-aminomethyl-5-methylhexanoic acid 8, whilst (S)-3-aminomethyl-5- methylhexanoic acid isobutyl ester 9 and (S)-3-aminomethyl-5-methylhexanoic acid isopropyl ester 10 are new compounds reported for the first time in our process. The present work describes the formation, synthesis and characterization of these impurities. © ARKAT USA, Inc.