Resolution of intermediates in the synthesis of substantially pure bicalutamide

US6593492B1 · kind B1 · utility

Assignee

• Nobex Corporation · US

Inventors

• Nnochiri Ekwuribe · Cary, US
• Kenneth D. James · Reading, GB

Key dates

• Filing date: Oct 25, 2000
• Grant date: Jul 15, 2003
• Expiry date: Mar 9, 2021

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07B2200/07
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A methods of preparing a substantially pure enantiomer of an acylanilide such as Casodex® (bicalutamide) and/or its derivatives includes resolving an intermediate compound having the structure of Formula I: whereinR1 is alkyl or haloalkyl having up to 4 carbons;R2 is alkyl having up to 6 carbon atoms;R3 is a direct link or alkyl having up to 6 carbon atoms;R4 is alkyl, alkenyl, hydroxyalkyl or cycloalkyl each of up to 6 carbons; or R4 is phenyl which bears one, two or three substituents independently selected from hydrogen, halogen, nitro, carboxy, carbamoyl and cyano, and alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenyl, phenylthio, phenylsulphinyl and phenylsulphonyl; or R4 is naphthyl; or R4 is a 5- or 6-membered saturated or unsaturated heterocyclic which contains one, two or three heteroatoms selected from oxygen, nitrogen and sulfur, which heterocyclic may be a single ring or may be fused to a benzo-ring, and which heterocyclic is unsubstituted or bears one or two halogen, cyano or amino, or a…