CN103562209A - 一种制备普拉格雷的方法及普拉格雷盐酸盐新晶型 - Google Patents
一种制备普拉格雷的方法及普拉格雷盐酸盐新晶型 Download PDFInfo
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- CN103562209A CN103562209A CN201280026521.3A CN201280026521A CN103562209A CN 103562209 A CN103562209 A CN 103562209A CN 201280026521 A CN201280026521 A CN 201280026521A CN 103562209 A CN103562209 A CN 103562209A
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- C07D495/04—Ortho-condensed systems
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
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Abstract
Description
Claims (13)
- 权 利 要 求 书1、 一种制备普拉格雷的方法, 其方法包:化合物: . 其中 R R2和 R3各自独立地为 CrC1Q的烷基。
- 2、 根据权利要求 1所述的方法, 所述的溶剂为丙酮、 丁酮或其组合。
- 3、 根据权利要求 1-2任一所述的方法, 所述乙酰化试剂为乙酰氯、 乙酰 溴、 乙酸酐或其组合。
- 4、 根据权利要求 1-3任一所述的方法, 所述碱为叔胺、 仲胺, 二乙胺、 三乙胺或其组合。
- 5、 根据权利要求 1-4任一所述的方法, 所述乙酰化反应在乙酰化催化剂 存在下进行, 所述乙酰化催化剂为 4-二烷基氨基吡啶, 其中烷基为 C<sub>r</sub>C<sub>6</sub>的 烷基或甲基。6、 根据权利要求 1-5任一所述的方法, 所述式 III所示化合物通过式 IV 所示化合物与式 发生缩合反应, 和纯化后制得;IV V其中, 式 V所示化合物中的 R为羟基保护基团。 7、 根据权利要求 6所述的方法, 所述纯化为用丙酮与水的混合溶剂重¾曰曰。8、 根据权利要求 7所述的方法, 所述丙酮与水的混合溶剂中丙酮与水 的体积比为由 0.5:1到 3:1, 或者为由 0.8:1到 2.5:1, 或者为由 0.9:1到 2.1:1, 或者为由 0.9:1到 1.1:1, 或者为由 1.9:1到 2.1:1, 或者为 1:1, 或者为 2:1。9、 一种普拉格雷盐酸盐晶型,其晶型为晶型 HI, 晶型 H2或晶型 H3, a) 其所述晶型 HI 的 X-射线粉末衍射图中在 2 Θ为 18.56和 24.46 度 +/-0.3度的位置有峰;b) 其所述晶型 H2的 X-射线粉末衍射图中在 1 Θ为 18.00、 23.76和 24.54度+/-0.3度的位置有峰; 或c) 其所述晶型 H3 的 X-射线粉末衍射图中在 2 Θ为 14.34和 25.66 度 +/-0.3度的位置有峰。10、 根据权利要求 9 所述晶型为晶型 Hl, 其 X-射线粉末衍射图中大约 在 2 Θ为 14.02、 15.92、 18.56、 23.66、 24.46、 25.92 和 26.62 度 +/-0.3 度的位置有峰。11、 根据权利要求 9 所述晶型为晶型 HI, 其 X-射线粉末衍射图中大约 在 2 Θ为 8.02、 8.46、 10.28、 12.34、 12.88、 13.38、 14.02、 14.36、 15.92、 17.36、 18.56、 18.86、 20.54、 22.04、 23.66、 24.46、 25.92、 26.62、 28.3、 29.46和 30.7度 +/-0.3度的位置有峰。12、 根据权利要求 9 所述晶型为晶型 H2, 其 X-射线粉末衍射图中大约 在 2 Θ为 14.06、 16.00、 18.00、 23.76、 24.54、 26.0和 26.7度 +/-0.3度 的位置有峰。13、 根据权利要求 9 所述晶型为晶型 H2, 其 X-射线粉末衍射图中大约 在 2 Θ为 8.54、 10.32、 11.66、 12.40、 12.94、 14.06、 16.00、 17.42、 18.00、 18.64、 18.94、 21.80、 22.16、 23.76、 24.54、 26.0、 26.7、 28.3、 29.6、 30.24和 34.98度 +/-0.3度的位置有峰。14、 根据权利要求 9 所述晶型为晶型 H3, 其 X-射线粉末衍射图中大约 在 2 Θ为 13.38、 13.78、 14.34、 16.06、 21.48、 22.06 和 25.66 度 +/-0.3 度的位置有峰。 15、 根据权利要求 9 所述晶型为晶型 H3, 其 X-射线粉末衍射图中大约 在 2 Θ为 7.98、 12.86、 13.38、 13.78、 14.34、 16.06、 17.12、 18.66、 20.52、 21.48、 22.06、 23.70、 25.66、 27.14、 27.64、 28.32 和 29.44 度 +/-0.3度的位置有峰。
- 16、 一种普拉格雷盐酸盐的结晶方法, 其方法包含溶解普拉格雷盐酸盐 於良溶剂形成溶液, 将该溶液缓慢滴入不良溶剂中析出晶体, 所述良溶剂为 醇类溶剂、 羧酸类溶剂或其组合, 所述不良溶剂为醚溶剂、 芳烃溶剂、 酯类 溶剂、 烷烃类溶剂或其组合。
- 17、 根据权利要求 16 所述的结晶方法, 所述良溶剂为醇类溶剂, 或者 为甲醇、 乙醇、 正丙醇、 异丙醇、 正丁醇或其组合, 所述不良溶剂为酯类溶 剂或乙酸乙酯。
- 18、 根据权利要求 16所述的结晶方法, 所述良溶剂为乙酸, 所述不良 溶剂为酯类溶剂或乙酸乙酯。
- 19、 根据权利要求 16所述的结晶方法, 所述良溶剂为乙酸, 所述不良 溶剂为芳烃类溶剂或甲苯。
- 20、 根据权利要求 16所述的结晶方法, 所述良溶剂为乙酸, 所述不良 溶剂为烷烃类溶剂或正己烷。
- 21、 根据权利要求 16所述的结晶方法, 所述良溶剂为乙酸, 所述不良 溶剂为醚类溶剂或甲基叔丁基醚。
- 22、 权利要求 9-15任一所述的普拉格雷盐酸盐晶型用于预防或治疗由血 栓或栓塞所引起的疾病。
- 23、 一种预防或治疗由血栓或栓塞所引起的疾病方法, 其方法包含给予 有該疾病的病人如权利要求 9-15任一所述的普拉格雷盐酸盐晶型。
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CN105669696B (zh) * | 2014-11-21 | 2019-03-26 | 四川海思科制药有限公司 | 一种盐酸普拉格雷化合物 |
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US8937053B2 (en) | 2015-01-20 |
CN103562209B (zh) | 2016-03-02 |
CN102838618A (zh) | 2012-12-26 |
WO2012175031A1 (zh) | 2012-12-27 |
US20140155351A1 (en) | 2014-06-05 |
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