Solid forms of an antiviral compound

• US 9,630,972 B2
• Filed: 06/08/2015
• Issued: 04/25/2017
• Est. Priority Date: 06/11/2014
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Lapina, Olga Viktorovna, Shi, Bing, Wang, Fang, Wolckenhauer, Scott Alan
• Primary Examiner(s): STOCKTON, LAURA LYNNE
• Application Number:
  US14/733,101
• Publication Number:
  US 20150361085A1
• Time in Patent Office: 687 Days
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 491/052 the oxygen-containing ring being six-membered

Abstract

Crystalline solid forms of methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (Compound I) were prepared and characterized in the solid state:

Also provided are processes of manufacture and methods of using these crystalline forms.

Claims

1. Crystalline methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′

,3′

;

6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate bis-hydrochloride (Compound I bis-HCl Form II) characterized by an X-ray powder diffractogram comprising the following peaks;

6.1, 7.3, and 9.6 °

2θ

±

0.2 °

2θ

, as determined on a diffractometer using Cu—

Kα

radiation at a wavelength of 1.5406 Å

.

2. Compound I bis-HCl Form II according to claim 1, wherein the diffractogram further comprises peaks at 3.6 and 10.9 °

2θ

±

0.2 °

2θ

.

3. Compound I bis-HCl Form II according to claim 1, wherein the diffractogram is substantially as shown in FIG. 4.

4. Compound I bis-HCl Form II according to claim 1, characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 186°

C.

5. Compound I bis-HCl Form II according to claim 4, wherein the DSC curve is substantially as shown in FIG. 5.

6. Crystalline methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′

,3′

;

6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate bis-hydrochloride (Compound I bis-HCl Form III) characterized by an X-ray powder diffractogram comprising the following peaks;

7.2 and 7.6 °

2θ

±

0.2 °

2θ

, as determined on a diffractometer using Cu—

Kα

radiation at a wavelength of 1.5406 Å

.

7. Compound I bis-HCl Form III according to claim 6, wherein the diffractogram further comprises peaks at 3.8 and 11.4 °

2θ

±

0.2 °

2θ

.

8. Compound I bis-HCl Form III according to claim 6, wherein the diffractogram is substantially as shown in FIG. 7.

9. Compound I bis-HCl Form III according to claim 6, characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 189°

C.

10. Compound I bis-HCl Form III according to claim 9, wherein the DSC curve is substantially as shown in FIG. 8.