Process for the synthesis of 2′-O-substituted pyrimidines and oligomeric compounds therefrom

US6642367B2 · kind B2 · utility

Assignee

• Isis Pharmaceuticals, Inc. · US

Inventors

• Phillip Dan Cook · Carlsbad, US
• Yogesh S. Sanghvi · Encinitas, US
• Kelly G. Sprankle · Vista, US
• Bruce Ross · Carlsbad, US
• Rich Griffey · Vista, US
• Robert H. Springer · Wyckoff, US

Key dates

• Filing date: Dec 22, 2000
• Grant date: Nov 4, 2003
• Expiry date: Dec 22, 2020

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/582
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2′ and 5′ positions. Monomeric sub-units having these modifications may be further modified at the 2′ position. Improved processes for the synthesis of 2′-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2′-anhydropyrimidine nucleoside or a 2S,2′-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.