Preparation of C22-alkyl derivative of digoxin

US3981862A · kind A · utility

Assignee

• Boehringer Mannheim GmbH · DE

Inventors

• Wolfgang Voigtlander · Viernheim, DE
• Fritz Kaiser · Lampertheim, DE
• Wolfgang Schaumann · Heidelberg, DE
• Kurt Stach

Key dates

• Filing date: Mar 14, 1975
• Grant date: Sep 21, 1976
• Expiry date: Mar 14, 1995

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07J19/005
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A process for the preparation of a C22-alkyl-derivative of digoxin of the formula ##SPC1## In which PA1 R.sub.1 is an alkyl radical containing up to 4 carbon atoms, PA1 R.sub.2 and R.sub.3 are selected from the group consisting of hydrogen, acyl, benzyl, carbobenzoxy, trimethylsilyl, tetrahydropyranyl or phosphonoacyl radicals or together form an alkylidene radical, Comprising reacting a compound of the formula ##SPC2## With an alkyl iodide of the formula R.sub.1 I in the presence of a strongly polar aprotic solvent and an alkali metal hydride. If R.sub.2 and R.sub.3 are other than hydrogen they can subsequently be replaced by hydrogen by hydrolysis or hydrogenation. The product can be .alpha.- or .beta.-methylated to produce compounds of high resorption and low toxicity.