Preparation of (S)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes

US6329542A · kind A · utility

Assignee

• Bristol-Myers Squibb Company · US

Inventors

• Jollie D. Godfrey, Jr. · Lawrenceville, US
• David Kronenthal · Yardley, US
• Mark D. Schwinden · Holland, US
• Sushil K. Srivastava
• Keith Ramig · Orange, US
• John J. Venit · New Brunswick, US
• Paul Jass · Charles City, US
• Saibaba Racha · Smithtown, US
• John L. Dillon, Jr. · El Paso, US
• Nachimuthu Soundararajan · Kendall Park, US
• Gerald L. Powers · New Brunswick, US
• Atul S. Kotnis · Kendall Park, US

Key dates

• Filing date: Oct 12, 2000
• Grant date: Dec 11, 2001
• Expiry date: Oct 12, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D317/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The glycinamide of the formula ##STR1## is reacted with the dioxolane of the formula ##STR2## wherein L is a leaving group such as iodo, bromo, alkylsulfonyloxy, or arylsulfonyloxy to give the dioxolane of the formula ##STR3## Treating the dioxolane of formula III under aqueous refluxing conditions followed by exchanging the dioxolane acetal with a dimethoxy acetal and introduction of the methyl ester gives (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester which is an intermediate in the preparation of the dual inhibitor [4S-[4.alpha.(R*),7.alpha.,10a.beta.]]-octahydro-4-[(2-mercapto-1-oxo-3-ph enylpropyl)-amino]-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid. Also disclosed are storage stable salts of (S)-2-amino-6, 6-dimethoxyhexanoic acid, methyl ester.