Crystal of arylethenesulfonamide derivative and preparation process thereof

1. An α-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethene-sulfonamide in substantially pure form.

2. An α-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethene-sulfonamide, characterized by having a melting point of from 196 to 198° C. and main peaks in the vicinity of lattice spacings of 12.00, 9.52, 4.77, 4.34 and 4.08 angstroms in the powder X-ray diffraction spectrum obtained using a Cu—Kα line.

3. The α-type crystal according to claim 2 , characterized by having the lattice spacings and relative intensities shown in Table 9 in the powder X-ray diffraction spectrum obtained using a Cu—Kα line.

TABLE 9

relative

lattice spacing/Å

intensity

lattice spacing/Å

relative intensity

13.42

slightly strong

4.23

strong

12.00

strong

4.08

strong

9.52

strong

3.87

slightly strong

7.46

medium

3.65

slightly strong

6.72

medium

3.46

slightly strong

5.43

medium

3.31

medium

4.77

strong

3.03

medium

4. A β-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethene-sulfonamide in substantially pure form.

5. A β-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethene-sulfonamide, characterized by having a melting point of 231 to 233° C. and main peaks in the vicinity of lattice spacings of 11.65 and 4.66 angstroms in the powder X-ray diffraction spectrum obtained using a Cu—Kα line.

6. The β-type crystal according to claim 5 , characterized by having the lattice spacings and relative intensities shown in Table 10 in the powder X-ray diffraction spectrum obtained using a Cu—Kα line.

TABLE 10

relative

lattice spacing/Å

intensity

lattice spacing/Å

relative intensity

11.65

strong

4.09

medium

9.65

medium

3.99

slightly strong

8.60

medium

3.88

slightly strong

5.13

slightly strong

3.69

slightly strong

4.79

medium

3.41

medium

4.66

strong

3.17

medium

4.36

medium

3.08

medium

4.22

slightly strong

7. A γ-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethene-sulfonamide in substantially pure form.

8. A γ-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethene-sulfonamide, characterized by having a melting point of 251 to 254° C. and main peaks in the vicinity of lattice spacings of 11.10, 4.92, 4.67, 4.23, 4.18, 4.10, 3.47 and 3.44 angstroms in the powder X-ray diffraction spectrum obtained using a Cu—Kα line.

9. A γ-type crystal according to claim 8 , characterized having the lattice spacings and relative intensities shown in Table 11 in the powder X-ray diffraction spectrum obtained using a Cu—Kα line.

TABLE 11

relative

lattice spacing/Å

intensity

lattice spacing/Å

relative intensity

11.10

strong

4.51

slightly strong

9.24

medium

4.23

strong

8.65

slightly strong

4.18

strong

4.92

strong

4.10

strong

4.87

slightly strong

3.47

strong

4.78

slightly strong

3.44

strong

4.67

strong

10. A preparation process of the α-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide according to claim 2 or claim 3 , characterized by exerting potassium hydroxide or potassium carbonate to (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide, a salt thereof, a solvate thereof or a solvate of a salt thereof in an ethanol-water mixed solvent, dissolving therein, and then crystallizing out of the solution in a water-ethanol mixed solvent having a ratio of water to ethanol of 1:12.5 or more.

11. A preparation process of the α-type crystal of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide according to claims 2 or claim 3 , characterized by exerting potassium hydroxide to (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin -2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide 0.4 ethyl acetate or a (E)-N-[6-methoxy -5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide monoethanolate in an ethanol-water mixed solvent, dissolving therein, and then crystallizing out of the solution in a water-ethanol mixed solvent having a ratio of water to ethanol of 1:12.5 or more.

12. (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide ethyl acetate.

13. (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl )pyrimidin-4-yl]-2-phenylethenesulfonamide 0.4 ethyl acetate.

14. (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide ethanolate.

15. (E)-[6-methoxy-5-(2-methoxphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide monoethanolate.