阅读说明：本技术 一种食欲素受体拮抗剂的晶型及其制备方法和用途 (Crystal form of orexin receptor antagonist and preparation method and application thereof ) 是由 陈敏华 张炎锋 黄春香 张晓宇 于 2018-07-31 设计创作，主要内容包括：一种化合物Lemborexant的晶型及其制备方法,含有该晶型的药物组合物,以及该晶型在制备食欲素受体拮抗剂、治疗失眠症和不规则睡眠-觉醒节律障碍药物制剂中的用途。提供的化合物Lemborexant的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="606" wi="623" file="DDA0002323472750000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(A crystal form of a compound Lemborexant, a preparation method thereof, a pharmaceutical composition containing the crystal form and application of the crystal form in preparing an orexin receptor antagonist and a pharmaceutical preparation for treating insomnia and irregular sleep-wake dysrhythmia. The provided crystal form of the compound Lemborexant has one or more improved properties compared with the prior art, and has important value on the optimization and development of the medicine in the future.)

A crystal form CS2 of E-2006, characterized in that an X-ray powder diffraction pattern thereof has characteristic peaks at 2 theta values of 7.8 DEG + -0.2 DEG, 15.6 DEG + -0.2 DEG, and 11.4 DEG + -0.2 deg.

Crystalline form CS2 according to claim 1, characterized by an X-ray powder diffraction pattern having characteristic peaks at 1 or 2 or 3 of 12.5 ° ± 0.2 °, 21.3 ° ± 0.2 °, 27.3 ° ± 0.2 ° 2 Θ values.

Crystalline form CS2 according to claim 1, characterized by an X-ray powder diffraction pattern having characteristic peaks at 1 or 2 or 3 of 24.0 ° ± 0.2 °, 19.4 ° ± 0.2 °, 22.3 ° ± 0.2 ° 2 Θ values.

A method of preparing the crystalline form CS 2E-2006 of claim 1, characterized in that the method comprises:

(1) dissolving a compound (I) raw material in a positive solvent to prepare a solution containing the compound (I), slowly dripping an anti-solvent into the solution, and stirring for crystallization to obtain the compound (I); or

(2) Dissolving a compound (I) raw material in a ketone solvent, and slowly volatilizing to obtain the compound (I); or

(3) Dissolving the raw material of the compound (I) in a nitrile solvent, adding ionic liquid for induction, and slowly volatilizing to obtain the compound.

The process according to claim 4, wherein the normal solvent in the process (1) is an alcoholic solvent, and the anti-solvent is water; the ketone solvent in the method (2) is acetone; in the method (3), the nitrile solvent is acetonitrile, and the ionic liquid is 1-ethyl-3-methylimidazole methyl sulfate, 1-ethyl-3-methylimidazole hexafluoroantimonate or 1, 3-dimethylimidazole dimethyl phosphate.

The process according to claim 5, wherein the alcoholic solvent in the process (1) is methanol.

A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form CS2 of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

Use of the crystalline form CS2 as claimed in claim 1 in the manufacture of a medicament for an orexin receptor antagonist.

Use of the crystalline form CS2 as claimed in claim 1 in the manufacture of a medicament for the treatment of insomnia and/or irregular sleep-wake dysrhythmia.