Synthesis of purine nucleosides

• US 9,045,520 B2
• Filed: 06/07/2012
• Issued: 06/02/2015
• Est. Priority Date: 12/23/2008
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Chun, Byoung-Kwon, Du, Jinfa, Rachakonda, Suguna, Ross, Bruce, Sofia, Michael Joseph, Pamulapati, Ganapati Reddy, Chang, Wonsuk, Zhang, Hai-Ren, Nagarathnam, Dhanpalan
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US13/491,437
• Publication Number:
  US 20120316327A1
• Time in Patent Office: 1,090 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical
• CPC Class Codes: C07H 19/167 with ribosyl as the saccharide radical
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/213 containing cyclic phosphate
• CPC Class Codes: C07H 5/02 to halogen
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

Claims

1. A compound of formula IV:

3. The compound of claim 1, wherein R⁵ is H.

2. A compound of formula V:

4. A process for preparing a compound of formula IV, wherein said process comprises:

(a) stereoselective reduction of a compound of formula III using a hydride reducing agent to provide a mixture comprising a compound of formula IV and a compound of formula IV-α

;