Crystalline forms of thienopyrimidine derivative
The present invention provides a production method of a thienopyrimidine derivative or a salt thereof which has a gonadotropin releasing hormone (GnRH) antagonistic action with high quality in high yield. The present invention provides a method of producing a thienopyrimidine derivative, which comprises reacting 6-(4-aminophenyl)-1-(2,6-difluorobenzyl) -5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)thieno[2,3-d]pyrimidine -2,4(1H,3H)-dione or salt thereof, 1,1′-carbonyldiimidazole or a salt thereof and methoxyamine or a salt thereof, and the like.
1. A crystalline form of a tetrahydrofuran solvate of 1-{4-[1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea that exhibits an X-ray powder diffraction pattern having 2-theta (2θ) peaks at approximately 7.285°, 10.597°, and 15.292.
2. The crystalline form of claim 1 that exhibits an X-ray powder diffraction pattern further having 2-theta (2θ) peaks at approximately 8.302° and 13.605°.
3. The crystalline form of claim 2 that exhibits an X-ray powder diffraction pattern further having 2-theta (2θ) peaks at approximately 18.792°, 23.059°, 25.144°, and 29.294°.
4. A crystalline form of a tetrahydrofuran solvate of 1-{4-[1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea that exhibits an X-ray powder diffraction pattern having peaks expressed in d values (Å) at approximately 12.125, 8.342, and 5.790.
5. The crystalline form of claim 4 that exhibits an X-ray powder diffraction pattern further having peaks expressed in d values (Å) at approximately 10.642 and 6.504.
6. The crystalline form of claim 5 that exhibits an X-ray powder diffraction pattern further having peaks expressed in d values (Å) at approximately 4.718, 3.854, 3.539, and 3.047.
7. A crystalline form of a tetrahydrofuran solvate of 1-{4-[1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea that exhibits an X-ray powder diffraction pattern having 2-theta (2θ) peaks and peaks expressed in d values (Å) at approximately:
2θ (°)
d value (Å)
7.285
12.125
8.302
10.642
10.597
8.342
13.605
6.504
15.292
5.790
18.792
4.718
23.059
3.854
25.144
3.539
29.294
3.047.
8. A crystalline form of a tetrahydrofuran solvate of 1-{4-[1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 1 .