IP Library › Granted Patent US 8,193,181
Granted Patent B2
US 8,193,181 · App. 12/676,075 · Granted Jun 5, 2012

Xinafoate salt of N4-(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy) phenyl]2,4-pyrimidinediamine

Assignee: Rigel Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 8,193,181
App. No.
12/676,075
Granted
Jun 5, 2012
Kind
B2
Abstract

The present invention relates to the xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine. This compound is a suitable drug substance and is useful in the treatment of conditions including asthma.

Claims (9)

1. A xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine.

2. The xinafoate salt of claim 1 having shifts at about −69.2, −72.4 and −164.0 ppm when characterized by fluorine solid state NMR referenced to an external sample of trifluoroacetic acid (50% by volume in H 2 O) assigned a resonance at −76.54 ppm.

3. A pharmaceutical composition comprising the xinafoate salt of claim 1 and a pharmaceutically acceptable excipient.

4. A method of treating asthma in a mammal, the method comprising administering to the mammal in need thereof a therapeutically effective amount of the xinafoate salt of claim 1 .

5. A process for preparing the xinafoate salt of claim 1 comprising dissolving N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine and between 1 and 1.1 molar equivalents 1-hydroxy-2-naphthoic acid in the minimum amount of a suitable organic solvent and cooling the solution slowly, optionally with stirring, until the salt precipitates from the solution.

6. The process of claim 5 wherein the solvent is acetone, acetonitrile or methyl ethyl ketone (MEK), each optionally containing a small amount of water.

7. The process of claim 6 wherein the solvent is methyl ethyl ketone containing about 5% by volume of water.

8. The compound of claim 1 formulated as a dry powder for administration from a dry powder inhaler.

9. A product comprising a dry powder inhaler and a xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine formulated as a dry powder for administration from a dry powder inhaler.

Assignments (4)
SECURITY INTEREST Recorded May 8, 2026
From: RIGEL PHARMACEUTICALS, INC.
To: MIDCAP FUNDING IV TRUST
Reel/Frame 075576/0880 →
SECURITY INTEREST Recorded Aug 25, 2022
From: RIGEL PHARMACEUTICALS, INC.
To: MIDCAP FINANCIAL TRUST
Reel/Frame 061327/0712 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 17, 2011
From: TAYLOR, STEFAN COLIN JOHN
To: PFIZER LIMITED
Reel/Frame 026456/0976 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 17, 2011
From: PFIZER LIMITED
To: RIGEL PHARMACEUTICALS, INC.
Reel/Frame 026457/0048 →
Continuity (2)
Provisional Application 60970030 · Sep 5, 2007
Related Publication 20100204232A1 · Aug 12, 2010