Synthesis of antiviral compound

• US 9,718,807 B2
• Filed: 08/04/2016
• Issued: 08/01/2017
• 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:
  US15/228,825
• Publication Number:
  US 20160340345A1
• Time in Patent Office: 362 Days
• 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 compound of formula (iii′

);

2. A compound according to formula (iv′

);

3. The compound according to claim 2, wherein the compound of formula (iv′

) is a hydrate according to the formula;

4. The compound according to claim 3, wherein q is a number between 0 and 6.

5. Crystalline compound of formula iv′

(Form I) according to claim 2 characterized by an X-ray powder diffractogram comprising the following peaks;

7.1, 8.2, 10.8 °

2θ

±

0.2 °

2θ

, as determined on a diffractometer using Cu—

K_α

radiation at a wavelength of 1.54060 Å

.

6. Crystalline Form I according to claim 5, wherein the diffractogram further comprises peaks at 11.1, 12.8, 14.1, 14.8, 16.1, 18.9, 24.5, 24.9, and 25.9 °

2θ

±

0.2 °

2θ

.

7. Crystalline Form I according to claim 5, wherein the diffractogram is substantially as shown in FIG. 1.

8. Crystalline compound of formula iv′

(Form II) according to claim 2 characterized by an X-ray powder diffractogram comprising the following peaks;

7.4, 9.4, and 11.6 2θ

±

0.2 °

2θ

as determined on a diffractometer at 25°

C. using Cu—

K_α

radiation at 1.54060 Å

.

9. Crystalline Form II according to claim 8, wherein the diffractogram further comprises peaks at 7.5, 14.9, 15.2, 22.5, 23.2, and 26.3 °

2θ

±

0.2 °

2θ

.

10. Crystalline Form II according to claim 8, wherein the diffractogram is substantially as shown in FIG. 2.