Process for the preparation of chiral tert-butyl 4-((1R,2S,5R)-6(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamido)piperidine-1-carb derivatives and (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide

US9604985B2 · kind B2 · utility

Assignee

• Merck Sharp & Dohme LLC · US

Inventors

• Steven P. Miller · Manalapan, US
• John Limanto · Jersey City, US
• Yong-Li Zhong · Edison, US
• Nobuyoshi Yasuda · Mountainside, US
• Zhijian Liu · Lo Wu, CN

Key dates

• Filing date: Jun 5, 2014
• Grant date: Mar 28, 2017
• Expiry date: Jun 5, 2034

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A process for the preparation of N-protected 6-(piperidin-4-ylcarbamoyl)piperidin-3-yl sulfonates of Formula (III): which comprises contacting a lactone of Formula (II): with an azacycloalkylamine of formula (II-Am): followed by contact with a sulfonyl halide of formula (II-Su): R4—SO2W (II-Su) in the presence of tertiary amine base, wherein PG1 and PG2 are amine protective groups; k, p and q are 0, 1, or 2, and W, R2, R3, R4, R5, R6, R7, R8, and R9 are defined herein. Additional embodiments add a series of process steps leading to the synthesis of 7-oxo-1,6-diazabicyclo[3.2.1]octanes suitable for use as β-lactamase inhibitors.