Synthesis of antiviral compound

• US 9,056,860 B2
• Filed: 03/13/2013
• Issued: 06/16/2015
• Est. Priority Date: 06/05/2012
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Scott, Robert William, Vitale, Justin Philip, Matthews, Kenneth Stanley, Teresk, Martin Gerald, Formella, Alexandra, Evans, Jared Wayne
• Primary Examiner(s): STOCKTON, LAURA LYNNE
• Application Number:
  US13/800,202
• Publication Number:
  US 20130324740A1
• Time in Patent Office: 825 Days
• Field of Search: 548/300.7
• 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: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present disclosure provides processes for the preparation of a compound of formula I:

which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates to compounds of formula I.

Claims

1. A process for making a compound of formula I:

2. The process according to claim 1, further comprising the step of in situ generation of the compound of formula (i),

3. The process according to claim 2, wherein the step of in situ generation of the compound of formula (i) and step (A) are carried out sequentially in one pot.

4. The process according to claim 2, where the borylation agent is selected from bis(pinacolato)diboron and bis(neopentylglycolato)diboron.

5. The process according to claim 4, where the borylation agent is bis(pinacolato)diboron.

6. The process according to claim 4, where the borylation agent is bis(neopentylglycolato)diboron.

7. The process according to claim 3, wherein X is Br and PG is tert-butoxycarbonyl.

8. The process according to claim 1, wherein the metal catalyst is PdCl₂[P(t-Bu)₂Ph]₂.

9. The process according to claim 1, wherein the metal catalyst is Pd(OAc)₂/2-dicyclohexylphosphino-2′

-methylbiphenyl.

10. The process according to claim 2, wherein the second base is a propionate salt.

11. The process according to claim 10, wherein the propionate salt is potassium propionate.

12. A process for making a compound of formula I:

13. A process for making a compound of formula I: