(2R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-[1,3]oxathiolane-2-carboxylic acid, 2S-isopropyl-5R-methyl-1R-cyclohexyl ester | 1235039-87-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (2R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-[1,3]oxathiolane-2-carboxylic acid, 2S-isopropyl-5R-methyl-1R-cyclohexyl ester
• 英文别名: 5-(4-Amino-2-oxo-1(2h)-pyrimidinyl)-1,3-oxathiolane-2-carboxylic acid 5-methyl-2-(1-methylethyl)cyclohexyl ester；(5-methyl-2-propan-2-ylcyclohexyl) 5-(4-amino-2-oxopyrimidin-1-yl)-1,3-oxathiolane-2-carboxylate
• CAS: 1235039-87-8
• 化学式: C₁₈H₂₇N₃O₄S
• 分子量: 381.496
• InChiKey: QMYKWNYBSBURDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  水杨酸 、 dipotassium hydrogenphosphate 、 (2R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-[1,3]oxathiolane-2-carboxylic acid, 2S-isopropyl-5R-methyl-1R-cyclohexyl ester 在 sodium borohydrid 作用下， 以 sodium hydroxide 、 水 为溶剂， 生成 4-amino-1-(2R-hydroxymethyl-[1,3]oxathiolan-5S-yl)-1H-pyrimidin-2-one salicylate
  参考文献：
  名称：

  Process for the diastereoselective synthesis of nucleoside analogues

  摘要：

  本发明涉及一种对映选择性工艺，用于制备式（I）的化合物，其中W为S，S.dbd.O，SO.sub.2或O；X为S，S.dbd.O，SO.sub.2或O；R.sub.1为氢或酰基，R.sub.2为嘌呤或嘧啶碱基或其类似物或衍生物。 ##STR1##

  公开号：

  US06051709A1

文献信息

• [EN] NOVEL PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE<br/>[FR] NOVEAU PROCEDE DE PREPARATION DE DERIVE DE CIS-NUCLEOSIDE
  申请人：MATRIX LAB LTD

  公开号：WO2011095987A1

  公开（公告）日：2011-08-11

  The present invention relates to an improved process for the preparation of cis-nucleoside derivative of formula-1 involving chlorination of the compound of formula-2 followed by reaction with compound of formula-3 in presence of a base to get compound of formula-4, reacting the compound of formula-4 with an alkyl halide (RiX) to get a quaternary ammonium salt then with cytosine derivative of formula-5 to provide the compound of formula-6, optionally de-protecting the compound of formula-6 to the compound of formula-7, reducing compound of formula-7 with metal catalyst in presence of a buffer solution, then adding an organic acid to get the compound of formula-8, and converting the compound of formula-8 to cis-nucleoside derivative of formula-1. The present invention further relates to novel cis-nucleoside derivative of formula-8. The present invention also relates to a pharmaceutical composition comprising cis-nucleoside derivative of formula-1 with excipients.

  本发明涉及一种改进的过程，用于制备式-1的顺式核苷衍生物，包括将式-2的化合物进行氯化，然后与式-3的化合物在碱的存在下发生反应得到式-4的化合物，将式-4的化合物与烷基卤化物（RiX）反应得到季铵盐，然后与式-5的胞嘧啶衍生物反应得到式-6的化合物，可选择性地去保护式-6的化合物得到式-7的化合物，用金属催化剂在缓冲溶液中还原式-7的化合物，然后加入有机酸得到式-8的化合物，并将式-8的化合物转化为式-1的顺式核苷衍生物。本发明还涉及新型式-8的顺式核苷衍生物。本发明还涉及一种包含式-1的顺式核苷衍生物与赋形剂的药物组合物。
• NOVEL PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
  申请人：Rama Shankar

  公开号：US20120295930A1

  公开（公告）日：2012-11-22

  The present invention relates to an improved process for the preparation of cis-nucleoside derivative of formula-1 involving chlorination of the compound of formula-2 followed by reaction with compound of formula-3 in presence of a base to get compound of formula-4, reacting the compound of formula-4 with an alkyl halide (RiX) to get a quaternary ammonium salt then with cytosine derivative of formula-5 to provide the compound of formula-6, optionally de-protecting the compound of formula-6 to the compound of formula-7, reducing compound of formula-7 with metal catalyst in presence of a buffer solution, then adding an organic acid to get the compound of formula-8, and converting the compound of formula-8 to cis-nucleoside derivative of formula-1. The present invention further relates to novel cis-nucleoside derivative of formula-8. The present invention also relates to a pharmaceutical composition comprising cis-nucleoside derivative of formula-1 with excipients.