Simplified procedure for the preparation of darunavir

US10774088B2 · kind B2 · utility

Assignee

• Janssen Sciences Ireland Unlimited Company · IE

Inventors

• Alfred Elisabeth Stappers · Oud-Turnhout, BE
• Yolande Lydia Lang · Vosselaar, BE
• Shane Barry Robinson · Midleton, IE

Key dates

• Filing date: Nov 16, 2017
• Grant date: Sep 15, 2020
• Expiry date: Nov 16, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D493/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention relates to an improved process for preparing [(1S,2R)-3-[[(4-aminophenyl)-sulfonyl](2-methyl-propyl)amino]-2-hydroxy-1-(phenylmethyl)-propyl]-carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester—which compound is also known under its INN as darunavir—by reacting carbonic acid 2,5-dioxo-1-pyrrolidinyl[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl]ester with 4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(2-methylpropyl)-benzenesulfonamide in ethanol as solvent. Furthermore said process allows for darunavir to be isolated immediately in its ethanolate form, i.e. darunavir monoethanolate, which is the marketed form of darunavir under the tradename Prezista™.