A multigram chemical synthesis of the γ-secretase inhibitor LY411575 and its diastereoisomers

…, K Simpson, GM Maharvi, T Golde, P Das

Index: Fauq, Abdul H.; Simpson, Katherine; Maharvi, Ghulam M.; Golde, Todd; Das, Pritam Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 22 p. 6392 - 6395

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Citation Number: 46

Abstract

An improved chemical synthesis of N-2 ((2S)-2-(3, 5-difluorophenyl)-2-hydroxyethanoyl)-N1- ((7S)-5-methyl-6-oxo-6, 7-dihydro-5H-dibenzo [b, d] azepin-7-yl)-l-alaninamide (LY411, 575, 9a), a known γ-secretase inhibitor, is described. The key synthetic steps, which used no chiral chromatography in the entire sequence, involved (1) improved microwave-assisted synthesis of a seven-membered lactam (±)-(5, 7-dihydro-6H-dibenz-[b, d] azepin-6-one 2, ...