IP Library Granted Patent US 8,362,253
Granted Patent B2
US 8,362,253 · App. 13/413,327 · Granted Jan 29, 2013

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

Inventors: John DeMattei (Berthoud, CO); Yushi Feng (Zionsville, IN); Cristian L. Harrison (Beverly, MA); Adam R. Looker (Cambridge, MA); Praveen Mudunuri (Waltham, MA); Stefanie Roeper (Medford, MA); Yuegang Zhang (Wayland, MA)
Assignee: Vertex Pharmaceutical Incorporated
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,362,253
App. No.
13/413,327
Granted
Jan 29, 2013
Kind
B2
Abstract

Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide are described herein, including crystalline forms thereof.

Claims (16)

1. A method of making crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide·XX, the method comprising:

dissolving N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide in XX and then cooling the solution of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and XX to provide crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide·XX, wherein XX is selected from 2-methylbutyric acid, propylene glycol, isobutyric acid, propionic acid, and 2-propanol.

2. A method of making crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.PEG 400.KOAc, the method comprising

dissolving N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide in a mixture of PEG and KOAc, and then cooling the resulting mixture to provide crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.PEG 400.KOAc.

3. A method of making crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.lactic acid, the method comprising dissolving N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and lactic acid in acetonitrile, and evaporating at least a portion of the acetonitrile to provide crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.lactic acid.

4. A method of making crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.H 2 O, the method comprising suspending N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide in H 2 O, and stirring the suspension of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and H 2 O to provide crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.H 2 O.

5. A method of making crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.besylate, the method comprising:

mixing N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, benzenesulfonic acid and an aprotic solvent; and

heating the mixture.

6. The method of claim 5 further comprising cooling the heated mixture and filtering the cooled mixture to provide crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.besylate.

7. The method of claim 5 , wherein the aprotic solvent comprises a solvent selected from an aprotic ether, an aprotic ester or a nitrile.

8. The method of claim 5 , wherein the aprotic solvent comprises a solvent selected from dimethoxy methane, t-butyl methyl ether, anisole, tetrahydrofuran, 2-methyltetrahydrofican, ethyl acetate, isopropyl acetate, n-butyl acetate, n-propyl acetate, t-butyl acetate, acetonitrile or mixtures thereof.

9. The method of claim 5 , wherein the aprotic solvent comprises a mixture of aprotic ether and aprotic ester solvents.

10. A method of making crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.besylate.H 2 O, the method comprising:

mixing N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.besylate, benzenesulfonic acid hydrate and an aprotic acetate solvent.

11. The method of claim 10 , wherein the aprotic acetate solvent comprises a mixture of ethyl acetate and isopropyl acetate.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Oct 14, 2016
From: MACQUARIE US TRADING LLC
To: VERTEX PHARMACEUTICALS INCORPORATED; VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
Reel/Frame 040357/0001 →
ASSIGNEE CHANGE OF ADDRESS Recorded Feb 17, 2016
From: VERTEX PHARMACEUTICALS INCORPORATED
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 037841/0274 →
SECURITY INTEREST Recorded Jul 10, 2014
From: VERTEX PHARMACEUTICALS INCORPORATED; VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
To: MACQUARIE US TRADING LLC
Reel/Frame 033292/0311 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 29, 2012
From: DEMATTEI, JOHN; FENG, YUSHI; HARRISON, CRISTIAN; LOOKER, ADAM; MUDUNURI, PRAVEEN; ROEPER, STEFANIE; ZHANG, YUEGANG
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 028279/0617 →
Continuity (3)
Continuation 12283702 · Sep 15, 2008
Provisional Application 60972605 · Sep 14, 2007
Related Publication 20120165372A1 · Jun 28, 2012