CRYSTAL FORM, PREPARATION METHOD AND INTERMEDIATE OF DIHYDROPYRIDO RING COMPOUND

• US 20180312512A1
• Filed: 11/02/2016
• Published: 11/01/2018
• Est. Priority Date: 11/04/2015
• Status: Active Application

• Current Assignee: QILU Pharmaceutical Company Limited
• Original Assignee: QILU Pharmaceutical Company Limited
• Inventors: HE, Haiying, ZHOU, Kai, LI, Xiaolin, WANG, Xiaofei, QIN, Dakun, WANG, Xingxing, YANG, Feifei, WANG, Zheng, LI, Zongbin
• Granted Patent: US 10,253,030 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 269/06 by reactions not involving the formation of carbamate groups
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Disclosed in the present disclosure are a crystal form of a dihydropyrido ring compound, and preparation method and intermediate thereof.

Claims

1. The crystal form I of Compound 1, comprising an X-ray powder diffraction pattern with characteristic diffraction peaks at the following 2θ

angles;

15.50±

0.2°

, 17.00±

0.2°

, 20.86±

0.2°

;

2. The crystal form I according to claim 1, comprising an X-ray powder diffraction pattern with characteristic diffraction peaks at the following 2θ

angles;

11.04±

0.2°

, 15.50±

0.2°

, 17.00±

0.2°

, 18.57±

0.2°

, 19.36±

0.2°

, 20.19±

0.2°

, 20.86±

0.2°

, 22.68±

0.2°

.

5. The crystal form I according to claim 1, comprising a DSC pattern as shown in FIG. 2.

6. The crystal form I according to claim 1, comprising a TGA pattern as shown in FIG. 3.

13. A medicament for treating HBV-related diseases comprising the crystal form I of Compound 1 according to claim 1.

14. A method of decreasing a level of hepatitis B virus (HBV), the method comprising:

contacting the HBV with the crystal form I of Compound 1 according to claim 1.

3. The crystal form I of Compound 1, comprising an X-ray powder diffraction pattern with characteristic diffraction peaks at the following 2θ

angles;

7.848°

, 10.489°

, 11.037°

, 12.875°

, 15.497°

, 16.995°

, 18.572°

, 19.360°

, 19.697°

, 20.192°

, 20.861°

, 22.676°

, 22.972°

, 23.225°

, 23.583°

, 23.940°

, 24.571°

, 24.886°

, 25.162°

, 25.476°

, 25.710°

, 26.405°

, 27.393°

, 28.237°

, 28.613°

, 29.007°

, 31.039°

, 32.892°

, 33.858°

, 34.095°

, 34.609°

, 35.000°

, 35.871°

, 36.538°

, 38.433°

;

4. The crystal form I of Compound 1, comprising an XRPD pattern as shown in FIG. 1,

12. The preparation method of the crystal form I of Compound 1 according to claim 4, comprising the following steps:

adding Compound 1 to a mixed solvent of ethyl acetate and petroleum ether for recrystallization, wherein the volume ratio of ethyl acetate to petroleum ether is 1;

0.5-2, preferably 1;

1;

or

adding Compound 1 to ethyl acetate and heating to reflux for dissolution, then dropwise adding n-heptane, and slowly cooling the mixture to 10°

C. to −

10°

C. for crystallization, wherein the volume ratio of ethyl acetate to n-heptane is 1;

0.5-2, preferably 1;

1.

7. A preparation method of Compound 1, comprising the following steps:

8. The preparation method according to claim 7, comprising the following steps:

9. The preparation method according to claim 7, comprising the following steps:

10. The preparation method according to claim 7, comprising the following steps:

11. The preparation method according to claim 7, comprising the following steps: