Crystalline forms of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine

Patent metadata

Field	Value
Publication number	US-11773079-B2
Application number	US-202117241972-A
Country	US
Kind code	B2
Filing date	Apr 27, 2021
Priority date	Jan 22, 2017
Publication date	Oct 3, 2023
Grant date	Oct 3, 2023

Abstract

The invention discloses a crystal of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine compound, a mesylate salt and crystal thereof, a preparation method thereof, a composition containing thereof, and a use thereof for inhibiting activity of mutant IDH2 and treating cancer.

First claim

What is claimed is:

1. Crystalline Form A of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of Formula I:

wherein the crystalline form is characterized by an X-ray powder diffraction pattern having X-ray powder diffraction peaks (°2θ) expressed by values at 10.1°, 16.1°, 17.5°, 18.9°, and 21.7°±0.2° (2θ).

2. The crystalline Form A according to claim 1 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction pattern having additional X-ray powder diffraction peaks (°2θ) expressed by values at 23.5°, 24.4°, and 26.2°±0.2°(2θ).

3. The crystalline Form A according to claim 1 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction pattern having additional X-ray powder diffraction peaks (°2θ) expressed by values at 22.4°, 22.8°, 23.5°, 24.0°, 24.4°, 26.2°, and 29.8°±0.2°(2θ).

4. The crystalline Form A according to claim 1 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction pattern having additional X-ray powder diffraction peaks (°2θ) expressed by values at 12.3°, 14.3°, 14.6°, 19.7°, 20.1°, 22.4°, 22.8°, 23.5°, 24.0°, 24.4°, 26.2°, and 29.8°±0.2°(2θ).

5. The crystalline Form A according to claim 1 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction pattern as shown in FIG. 1 .

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the crystalline Form A according to claim 1 .

7. A method for treating an isocitrate dehydrogenase 2 mutation-induced cancer in a subject, wherein the 1 method comprises administering to the subject in need thereof the crystalline Form A according to claim 1 .

8. The method according to claim 7 , wherein the isocitrate dehydrogenase 2 mutation-induced cancer is selected from the group consisting of glioblastoma, myelodysplastic syndrome, myeloproliferative neoplasm, acute myelogenous leukemia, sarcoma, melanoma, non-small cell lung cancer, chondrosarcoma, bile duct cancer, and angioimmunoblastic non-Hodgkin's lymphoma.

9. A process for preparing the crystalline Form A of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of Formula I according to claim 1 :

wherein the process comprises the following steps:
(1) at room temperature, dissolving 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of the Formula I below in at least one organic solvent selected from the group consisting of acetone, acetonitrile, methanol, ethanol, isopropanol, tert-butanol, tetrahydrofuran, and 1,4-dioxane, or a mixture thereof, to obtain a solution:

(2) concentrating the solution formed in step (1) above under reduced pressure; and
(3) drying the crystalline Form A of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of the Formula I above.

10. The process according to claim 9 , wherein the organic solvent is selected from the group consisting of tetrahydrofuran and 1,4-dioxane, or a mixture thereof.

11. A process for preparing the crystalline Form A of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of Formula I according to claim 1 :

wherein the process comprises the following steps:
(1) slurrying 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of the Formula I below in at least one organic solvent selected from the group consisting of dichloromethane, diethyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether, n-hexane, n-heptane, and n-octane, or a mixture thereof:

(2) filtering the slurry formed in step (1) above; and
(3) drying the crystalline Form A of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine of the Formula I above.

12. The process according to claim 11 , wherein the organic solvent is selected from the group consisting of dichloromethane, methyl tert-butyl ether, and n-heptane, or a mixture thereof.

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd
• Lianyungang Runzhong Pharmaceutical Co Ltd
• Centaurus Biopharma Co Ltd

Inventors

• Huang Ticong
• Xiao Huifeng
• Zhao Rui
• Liu Fei
• Wei Wei
• Xu Hongjiang
• Wang Xiaojin
• Wu Jingli

Classifications

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07C309/04

  containing only one sulfo group · CPC title