Methods of synthesis for 9-substituted hypoxanthine derivatives

US6849735B1 · kind B1 · utility

Assignee

• Merck Eprova AG · CH

Inventors

• Alvin J. Glasky · Tustin, US
• Heinrich Bollinger · Beringen, CH
• Hans Muller · Kirkland, US

Key dates

• Filing date: Jun 23, 2000
• Grant date: Feb 1, 2005
• Expiry date: Jun 23, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D473/30
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

An improved method of synthesis of a 9-substituted hypoxanthine derivative comprises the steps of: (1) reacting aminocyanacetamide with triethyl orthoformate to form an imidoester derivative of aminocyanacetamide; (2) forming a compound having a reactive amino group on a hydrocarbyl moiety, the hydrocarbyl moiety being linked through an amide group to a physiologically active moiety or an esterified derivative of a physiologically active moiety including therein an esterified benzoyl group; (3) reacting the imidoester with the compound having the reactive amino group on the hydrocarbyl moiety to form a derivative of aminoimidazole-4-carboxamide substituted at the 1-position with a hydrocarbyl moiety linked through an amide group to a physiologically active moiety including therein an optionally esterified benzoyl group; (4) forming the six-membered heterocyclic ring of the purine moiety of the hypoxanthine by reacting the derivative of 5-aminoimidazole-4-carboxamide formed in step (3) with triethyl orthoformate to form a 9-substituted hypoxanthine compound substituted at the 9-position with a hydrocarbyl moiety linked through an amide group to a physiologically active moiety includ…