Crystal form of brexpiprazole and preparation method therefor

Patent metadata

Field	Value
Publication number	US-10550109-B2
Application number	US-201716300301-A
Country	US
Kind code	B2
Filing date	May 12, 2017
Priority date	May 12, 2016
Publication date	Feb 4, 2020
Grant date	Feb 4, 2020

Abstract

Disclosed are a crystal form of brexpiprazole and a preparation method therefor. The X-ray powder diffraction pattern, which is detected with Cu—Kα radiation, of the crystal form of brexpiprazole has characteristic peaks at the positions where 2θ is about 9.1±0.2, 15.2±0.2, 15.7±0.2, 17.6±0.2, 18.1±0.2, 24.4±0.2. The crystal form I of brexpiprazole has a high purity, good stability and good reproducibility, and is suitable for industrial production.

First claim

The invention claimed is:

1. A crystal form I of brexpiprazole having a structure of formula I, wherein an X-ray powder diffraction pattern of the crystal form I comprises characteristic peaks of 9.1±0.2, 10.8±0.2, 14.9±0.2, 15.2±0.2, 15.7±0.2, 16.5±0.2, 17.6±0.2, 18.1±0.2, 18.6±0.2, 24.4±0.2 degrees 2θ,

2. The crystal form I of brexpiprazole of claim 1 , wherein the crystal form I has a crystal water endothermic peak at about 43° C.-72° C. and a melting endothermic peak at 179° C.-184° C. exhibited by a differential scanning calorimetry pattern.

3. The crystal form I of brexpiprazole of claim 1 , wherein the crystal form I has a water content of 3.0 wt. %-4.0 wt. %.

4. A method for preparing the crystal form I of brexpiprazole having the structure of formula I of claim 1 , comprising following steps:
(a) mixing brexpiprazole with a mixed solvent of ethanol and water at room temperature to prepare a suspension;
(b) adding acetic acid into the suspension of step (a) and heating to completely dissolved to obtain a clarified solution; and
(c) adding the clarified solution of step (b) into a sodium hydroxide solution to pH of 7-14 after cooling, precipitating solids, keeping stirring, filtering and drying to obtain the crystal form I of brexpiprazole.

5. The method of claim 4 , wherein a ratio of ethanol to water in step (a) is 2:3.

6. The method of claim 4 , wherein the clarified solution of step (b) is added into the sodium hydroxide solution to pH of 10-11 after cooling in step (c).

7. The crystal form I of brexpiprazole of claim 2 , wherein the crystal form I has a water content of 3.0 wt. %-4.0 wt. %.

Assignees

• Zhejiang Huahai Pharm Co Ltd
• Shanghai Aobo Pharmtech Inc Ltd

Inventors

• Jiao Yinglu
• Li Handa
• Wang Boyu
• Huang Luning
• Chen Xi
• Gu Hong

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D409/14 Primary

  containing three or more hetero rings · CPC title

• C07D409/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title