1-[6-amino-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-methylpyrazole-4-carboxamide;hydrate

• 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: 1-[6-amino-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-methylpyrazole-4-carboxamide;hydrate
• 化学式: C15H20N8O6
• 分子量: 408.37
• InChiKey: CDQVVPUXSPZONN-JQBAGTOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.26
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  188
• 氢给体数：
  6
• 氢受体数：
  11

文献信息

• POLYMORPH OF 2-[4-[(METHYLAMINO)CARBONYL]-1H-PYRAZOL-1-YL]ADENOSINE
  申请人：Farmak, a.s.

  公开号：US20140323712A1

  公开（公告）日：2014-10-30

  A new polymorph of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine (designated as polymorph E), characterized by an X-ray diffraction pattern of X-RPD showing the following reflections at 2 Theta=5.8°, 12.3°, 15.9°, 17.3°, 20.5°, 22.6°, 23.6°, 27.7°, and 29.2°, and further characterized by DSC showing marked endotherm in the range of 258 to 264° C., and further characterized by IR spectra, which is prepared by a procedure comprising the following operations: Mixing of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine with a polar aprotic solvent, preferably with dimethylsulfoxide, and heating to form a saturated solution; Cooling of the saturated solution with formation of a turbid solution of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine; Addition of the turbid solution of 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine to a protic solvent, preferably methanol, with separation of a gel-like precipitate; Heating of the separated gel-like precipitate in the protic solvent to the boil with formation of a suspension of polymorph E; Cooling of the suspension, isolation and drying of polymorph E.

  一种新的2-[4-[(甲基氨基)羰基]-1H-吡唑-1-基]腺苷的多晶形态（命名为多晶形态E），其X射线衍射图谱X-RPD显示在2Θ=5.8°，12.3°，15.9°，17.3°，20.5°，22.6°，23.6°，27.7°和29.2°处有以下反射，进一步通过DSC显示在258至264°C范围内有明显的吸热，以及进一步通过IR光谱表征，该多晶形态的制备包括以下操作：将2-[4-[(甲基氨基)羰基]-1H-吡唑-1-基]腺苷与极性无水溶剂混合，最好是二甲基亚砜，并加热形成饱和溶液；将饱和溶液冷却，形成2-[4-[(甲基氨基)羰基]-1H-吡唑-1-基]腺苷的混浊溶液；将混浊溶液加入至质子溶剂，最好是甲醇，分离出凝胶状沉淀；将分离的凝胶状沉淀在质子溶剂中加热至沸腾，形成多晶形态E的悬浮液；冷却悬浮液，分离和干燥多晶形态E。
• [EN] NEW POLYMORPH OF 2-[4-F(METHYLAMINO)CARBONYL]-1H-PYRAZOL-1-YL]ADENOSINE AND METHOD OF ITS PREPARATION<br/>[FR] NOUVEAU POLYMORPHE DE 2-[4-[(MÉTHYLAMINO)CARBONYL]-1H-PYRAZOL-1-YL]ADÉNOSINE ET SON PROCÉDÉ DE PRÉPARATION
  申请人：FARMAK A S

  公开号：WO2014177119A1

  公开（公告）日：2014-11-06

  A new polymorph of 2-[4-[(methylamino)carbonyl]-1 H-pyrazol-1- yl]adenosine (designated as polymorph E), of formula I, characterized by an X-ray diffraction pattern of X-RPD showing the following reflections at 2 Theta = 5.8°, 12.3°, 15.9°, 17.3°, 20.5°, 22.6°, 23.6°, 27.7°, and 29.2°, and further characterized by DSC showing marked endotherm in the range of 258 to 264 °C, and further characterized by IR spectra, which is prepared by a procedure comprising the following operations: • a. Mixing of 2-[4-[(methylamino)carbonyl]-1 H-pyrazol-1- yl]adenosine with a polar aprotic solvent, preferably with dimethylsulfoxide, and heating to form a saturated solution; • b. Cooling of the saturated solution with formation of a turbid solution of 2-[4: [(methylamino)carbonyl]-1 H-pyrazol-1- yl]adenosine; • c. Addition of the turbid solution of 2-[4-[(methylamino)carbonyl]-1 H-pyrazol-l-yl]adenosine to a protic solvent, preferably methanol, with separation of a gel-like precipitate; • d. Heating of the separated gel-like precipitate in the protic solvent to the boil with formation of a suspension of polymorph E; • e. Cooling of the suspension, isolation and drying of polymorph E.

  一种新的2-[4-[(甲基氨基)羰基]-1 H-吡唑-1-基]腺苷的多形态（命名为多形态E），化学式为I，其特征为X-射线衍射图谱X-RPD显示在2 Theta = 5.8°、12.3°、15.9°、17.3°、20.5°、22.6°、23.6°、27.7°和29.2°处具有以下反射，通过DSC表现为在258至264°C范围内明显的吸热，进一步通过IR光谱表征，该多形态通过以下操作制备： • a. 将2-[4-[(甲基氨基)羰基]-1 H-吡唑-1-基]腺苷与极性非质子溶剂混合，最好是二甲基亚砜，并加热形成饱和溶液； • b. 冷却饱和溶液，形成2-[4: [(甲基氨基)羰基]-1 H-吡唑-1-基]腺苷的混浊溶液； • c. 将2-[4-[(甲基氨基)羰基]-1 H-吡唑-1-基]腺苷的混浊溶液加入质子溶剂，最好是甲醇，分离出凝胶状沉淀； • d. 在质子溶剂中将分离的凝胶状沉淀加热至沸腾，形成多形态E的悬浮液； • e. 冷却悬浮液，分离和干燥多形态E。
• METHOD FOR THE PREPARATION OF 2-[4-[(METHYLAMINO)CARBONYL]-1-H-PYRAZOL-1-YL]ADENOSINE MONOHYDRATE
  申请人：FARMAK, A.S.

  公开号：US20140194615A1

  公开（公告）日：2014-07-10

  A method for the preparation of 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1-yl]adenosine monohydrate of formula I by reaction of 2-(4-methoxycarbonylpyrazol-1-yl) adenosine of formula III with a solution of methylamine in a non-aqueous solvent, optionally in combination with another inert solvent, to produce anhydrous 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1-yl]adenosine, which is converted to 2-[4-[(methylamino)carbonyl]-1-H-pyrazol-1-yljadenosine monohydrate of formula I by addition of water.

  通过将公式III的2-(4-甲氧羰基吡唑-1-基)腺苷与非水溶剂中的甲胺溶液反应，可制备公式I的2-[4-[(甲基氨基)羰基]-1-H-吡唑-1-基]腺苷一水合物的方法，可选地与另一种惰性溶剂结合，以产生无水2-[4-[(甲基氨基)羰基]-1-H-吡唑-1-基]腺苷，通过加水转化为公式I的2-[4-[(甲基氨基)羰基]-1-H-吡唑-1-基]腺苷一水合物。
• US9441006B2
  申请人：——

  公开号：US9441006B2

  公开（公告）日：2016-09-13