Crystal forms of 6-bromo-3-hydroxy-2-pyrazinecarboxamide

Patent metadata

Field	Value
Publication number	US-10519117-B2
Application number	US-201916293100-A
Country	US
Kind code	B2
Filing date	Mar 5, 2019
Priority date	Jun 9, 2015
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

The purpose of the present invention is to provide a method for producing 6-bromo-3-hydroxy-2-pyrazinecarboxamide in which the content ratio of impurities is reduced. This production method includes a step of obtaining 6-bromo-3-hydroxy-2-pyrazinecarboxamide crystal having diffraction angles expressed in degrees 2θ of 5.5, 20.1, 23.7, 26.7, 27.5, and 28.1° and/or diffraction angles expressed in degrees 2θ of 7.1, 21.4, 25.2, 25.7, 27.1, and 28.8° in powder X-ray diffraction.

First claim

The invention claimed is:

1. A type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide having powder X-ray diffraction angles (2θ) of 5.5°, 20.1°, 23.7°, 26.7°, 27.5° and 28.1°.

2. A method for producing a type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide, wherein the method comprises:
(1) adding anhydrous 3-hydroxy-2-pyrazinecarboxamide having powder X-ray diffraction angles (2θ) of 11.9°, 13.2°, 23.9°, and 26.7° to N,N-dimethylformamide to form a suspension;
(2) reacting the suspension formed in the adding above with bromine to produce a mixture; and
(3) obtaining a type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide having powder X-ray diffraction angles (2θ) of 5.5°, 20.1°, 23.7°, 26.7°, 27.5° and 28.1°.

3. The method of claim 2 , wherein the adding is performed in the presence of pyridine.

4. The method of claim 2 , wherein the method further comprises adding toluene to the mixture.

5. The method of claim 4 , wherein the toluene is added at a temperature in the range of 70° C. to 75° C.

6. The method of claim 5 , wherein the method further comprises adding water to the mixture.

7. The method of claim 6 , wherein the water is added at a temperature in the range of 38° C. to 45° C.

8. The method of claim 7 , wherein the mixture is cooled to 10° C.

9. The method of claim 8 , wherein the type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide is obtained by filtration.

10. A method for producing a type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide, wherein the method comprises:
(1) adding a type-B crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide having powder X-ray diffraction angles (2θ) of 7.1°, 21.4°, 25.2°, 25.7°, 27.1° and 28.8° to N,N-dimethylformamide in the presence of activated carbon to form a suspension;
(2) filtering the suspension formed in the adding above;
(3) washing the filter cake obtained in the filtering above with N,N-dimethylformamide;
(4) adding water to the combined filtrates formed in the filtering and the washing above to form a mixture; and
(5) obtaining a type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide having powder X-ray diffraction angles (2θ) of 5.5°, 20.1°, 23.7°, 26.7°, 27.5° and 28.1°.

11. The method of claim 10 , wherein the adding and the filtering are performed at a temperature of 50° C.

12. The method of claim 10 , wherein the adding of water is performed at a temperature of 50° C.

13. The method of claim 12 , wherein the mixture is cooled to 10° C.

14. The method of claim 13 , wherein the type-A crystal of 6-bromo-3-hydroxy-2-pyrazinecarboxamide is obtained by filtration.

Assignees

• Fujifilm Toyama Chemical Co Ltd

Inventors

• Uchida Tetsuro
• Uehara Sayuri
• Tsuzuki Takayoshi
• Okubo Yusuke
• Kobayashi Yuta
• KOSEKI Yu

Classifications

• C07D241/24 Primary

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title