2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-β-D-ribofuranosyl]-purine | 1266098-30-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-β-D-ribofuranosyl]-purine
• 英文别名: 2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-beta-D-ribofurano syl]-purine；[(2R,3S,5R)-3-(4-chlorobenzoyl)oxy-5-[2-chloro-6-(trimethylsilylamino)purin-9-yl]oxolan-2-yl]methyl 4-chlorobenzoate
• CAS: 1266098-30-9
• 化学式: C₂₇H₂₆Cl₃N₅O₅Si
• 分子量: 634.978
• InChiKey: WNDHTHBISAARJV-PWRODBHTSA-N

物化性质

• 沸点：
  684.9±65.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-β-D-ribofuranosyl]-purine 以86的产率得到克拉屈滨
  参考文献：
  名称：

  Org. Process Res. Dev. 2013, 17, 1419-1429

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氯-6-氨基嘌呤 、 1-氧乙酰基-3,5-二对氯苯甲酰基-2-脱氧-D-核糖 以63的产率得到2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-β-D-ribofuranosyl]-purine
  参考文献：
  名称：

  Org. Process Res. Dev. 2013, 17, 1419-1429

  摘要：

  DOI：

文献信息

• [EN] PROCESS FOR THE PREPARATION OF CLADRIBINE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE CLADRIBINE
  申请人：SCINOPHARM KUNSHAN BIOCHEMICAL TECHNOLOGY CO LTD

  公开号：WO2011020298A1

  公开（公告）日：2011-02-24

  A process for the preparation of cladribine of API grade is provided by direct coupling of O-protected 2-deoxy-ribofuranose with silylated 2-chloroadenine followed by deprotection of the resultant protected nucleoside in a separate step and then a purification step. Following the coupling, the desired N-9-glycosylated β-anomer of the nucleoside is directly isolated as a solid from the coupling reaction mixture by filtration in relatively high purity and yield, and it does not require purification.

  提供一种制备API级别的克拉德利宾的方法，通过保护O-2-去氧核糖与硅烷化的2-氯腺嘌呤直接偶联，然后在单独的步骤中去保护所得的保护核苷，然后进行纯化步骤。在偶联后，所需的核苷的N-9-糖基化β异构体可以通过过滤在相对高的纯度和收率下直接从偶联反应混合物中固态分离，而且不需要纯化。
• Process for the Preparation of Cladribine
  申请人：Henschke Julian Paul

  公开号：US20110046363A1

  公开（公告）日：2011-02-24

  A process for the preparation of cladribine of API grade is provided by direct coupling of O-protected 2-deoxy-ribofuranose with silylated 2-chloroadenine followed by deprotection of the resultant protected nucleoside in a separate step and then a purification step. Following the coupling, the desired N-9-glycosylated β-anomer of the nucleoside is directly isolated as a solid from the coupling reaction mixture by filtration in relatively high purity and yield, and it does not require purification.

  提供了一种制备API级别的克拉德利宾的工艺，即直接将O-保护的2-脱氧核糖与硅烷化的2-氯腺嘌呤进行偶联，然后在单独的步骤中去保护核苷酸产物，然后进行纯化。在偶联后，所需的核苷酸的N-9-糖基化β异构体可以通过过滤从偶联反应混合物中直接分离为固体，且纯度和收率相对较高，不需要进行纯化。
• PROCESS OF MAKING CLADRIBINE
  申请人：HENSCHKE Julian Paul

  公开号：US20120197010A1

  公开（公告）日：2012-08-02

  A method of making cladribine with an increased purity comprising: a) dissolving crude cladribine in a protic solvent in the presence of a base to form a solution comprising dissolved crude cladribine; b) maintaining the solution at an elevated temperature so that the solution is homogeneous until the amount of protected or partially protected nucleoside impurities in the solution is reduced to a pre-determined upper limit; and c) cooling the solution of step b) so that crystals of cladribine are formed and isolated.

  一种制备纯度增加的克拉德布林的方法，包括：a) 在碱的存在下，将粗克拉德布林溶解在质子溶剂中，形成包含溶解的粗克拉德布林的溶液；b) 将溶液保持在升高的温度下，使溶液均匀，直到溶液中受保护或部分受保护的核苷杂质的数量降低到预定的上限；和c) 冷却b步骤的溶液，使克拉德布林的晶体形成并分离。
• Process of making cladribine
  申请人：ScinoPharm (Kunshan) Biochemical Technology Co., Ltd.

  公开号：US08338586B2

  公开（公告）日：2012-12-25

  A method of making cladribine with an increased purity comprising: a) dissolving crude cladribine in a protic solvent in the presence of a base to form a solution comprising dissolved crude cladribine; b) maintaining the solution at an elevated temperature so that the solution is homogeneous until the amount of protected or partially protected nucleoside impurities in the solution is reduced to a pre-determined upper limit; and c) cooling the solution of step b) so that crystals of cladribine are formed and isolated.

  一种制备高纯度克拉德利宾的方法，包括：a) 在碱的存在下将粗克拉德利宾溶解于质子溶剂中，形成含有溶解的粗克拉德利宾的溶液；b) 将溶液保持在升高的温度下，以使溶液均匀，直到溶液中受保护或部分受保护的核苷杂质的量降低到预定的上限；以及c) 冷却步骤b)的溶液，使克拉德利宾晶体形成并被分离。
• Process for the preparation of cladribine
  申请人：ScinoPharm Taiwan, Ltd.

  公开号：US08232387B2

  公开（公告）日：2012-07-31

  A process for the preparation of cladribine of API grade is provided by direct coupling of O-protected 2-deoxy-ribofuranose with silylated 2-chloroadenine followed by deprotection of the resultant protected nucleoside in a separate step and then a purification step. Following the coupling, the desired N-9-glycosylated β-anomer of the nucleoside is directly isolated as a solid from the coupling reaction mixture by filtration in relatively high purity and yield, and it does not require purification.

  提供了一种制备API级别的克拉德霉素的方法，该方法通过保护O-2-去氧核糖与硅化2-氯腺嘌呤直接偶联，然后在单独的步骤中去保护所得的保护核苷，然后进行纯化步骤。在偶联后，所需的核苷的N-9-糖基化β异构体可以直接从偶联反应混合物中以相对较高的纯度和产率通过过滤固体分离，并且不需要纯化。