阅读说明：本技术 Acalabrutinib的新晶型及其制备方法和用途 (Novel crystal form of Acaraburtinib and preparation method and application thereof ) 是由 陈敏华 张炎锋 刘远 张龙 杨朝惠 于 2019-03-05 设计创作，主要内容包括：本发明涉及Acalabrutinib的新晶型及其制备方法,含有该晶型的药物组合物,以及该晶型在制备布鲁顿酪氨酸激酶抑制剂和治疗套细胞淋巴癌药物制剂中的用途。本发明提供的Acalabrutinib晶型比现有技术具有一种或多种改进的特性,对未来该药物的优化和开发具有重要价值。<Image he="553" wi="700" file="DDA0002268949770000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention relates to a novel crystal form of Acalabrutinib, a preparation method thereof, a pharmaceutical composition containing the crystal form, and application of the crystal form in preparation of Bruton tyrosine kinase inhibitors and pharmaceutical preparations for treating mantle cell lymphoma. Compared with the prior art, the Acalabastinib crystal form provided by the invention has one or more improved characteristics, and has important value for the optimization and development of the medicine in the future.)

A crystal form K1 of Acaraburtinib is characterized in that a Cu-K α radiation is used, and an X-ray powder diffraction pattern of the crystal form K1 has characteristic peaks at 2 theta values of 5.8 degrees +/-0.2 degrees, 9.5 degrees +/-0.2 degrees and 14.3 degrees +/-0.2 degrees.

Crystalline form K1 according to claim 1, further characterized by an X-ray powder diffraction pattern having characteristic peaks at 1, or 2, or 3 in the 2 Θ values of 13.8 ° ± 0.2 °, 12.8 ° ± 0.2 °, 18.4 ° ± 0.2 ° using radiation from Cu-K α.

Crystalline form K1 according to claim 1, further characterized by an X-ray powder diffraction pattern having characteristic peaks at 1, or 2, or 3 in the 2 Θ values of 16.3 ° ± 0.2 °, 6.9 ° ± 0.2 °, 11.5 ° ± 0.2 ° using radiation from Cu-K α.

A method for preparing form K1 according to claim 1, wherein the method is:

(1) adding Acalabastinib free alkali and acid into a mixed solvent of ketones and water, stirring, separating and drying to obtain a solid, adding the solid into water to form a suspension, adding an alkaline solution into the suspension, stirring, and separating to obtain a crystal form K1; or

(2) Adding the acarabretinib free base into an acidic solution, stirring, separating and drying the obtained solid, continuously transferring the solid into an alkaline solution, stirring, and separating to obtain a solid crystal form K1.

The production process according to claim 4, wherein in the process (1), the acid is maleic acid or fumaric acid, the basic solution is an aqueous solution of sodium hydroxide, and the ketone-based solvent is acetone, 2-butanone or methyl isobutyl ketone; in the method (2), the acidic solution is an aqueous hydrochloric acid solution, and the alkaline solution is an aqueous sodium hydroxide solution.

A pharmaceutical composition comprising a therapeutically effective amount of crystalline form K1 of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

Use of the crystalline form K1 as claimed in claim 1 in the manufacture of a medicament for the treatment of bruton's tyrosine kinase inhibitor.

Use of the crystalline form K1 according to claim 1 for the preparation of a medicament for the treatment of mantle cell lymphoma and/or chronic lymphocytic leukemia and/or macroglobulinemia and/or follicular lymphoma and/or diffuse large B-cell lymphoma and/or multiple myeloma