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Crystalline form of sodium (4R,12aS)-9-{[(2,4-difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate Disclosure Number: IPCOM000238311D
Publication Date: 2014-Aug-17
Document File: 2 page(s) / 113K

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        Crystalline form of sodium (4R,12aS)-9-{[(2,4- difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a- hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate

Disclosed hereinafter is a crystalline form of sodium (4R,12aS)-9-{[(2,4- difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H- pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate (referred herein as compound I)

Figure 1: a powder XRPD pattern of crystalline compound I:



*the peak marked by star relates to addition of Silicon internal standard.

XRPD peaks: 11.9, 13.1, 14.2, 16.6, 19.9, 22.9, 23.7, 24.5, and 27.0 degrees two theta ± 0.2 degrees two theta.

X-Ray Power Diffraction:

The analyses were performed on ARL (SCINTAG) powder X-Ray diffractometer model X'TRA equipped with a solid state detector. Copper radiation of 1.5418 Å was used. Scanning parameters: range: 2-40 degrees two-theta; scan mode: continuous scan; step size: 0.05°, and a rate of 3 deg/min.

Example 1: Preparation of crystalline form of Compound I (4R,12aS)-9-{[(2,4-difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo- 3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate (0.5g;
1.0 eq) was slurried at room temperature in THF (2.5 mL). The reaction mixture was

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warmed to reflux followed by dropwise addition of 2N NaOHaq (0.63 mL; 1.05eq). The obtained mixture was cooled to room temperature and stirred for overnight. The precipitate was collecte...