2,6-二氨基-3,5-二氢-7-(3-噻吩基甲基)-4H-吡咯并(3,2-d)嘧啶-4-酮盐酸盐 | 115787-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 中文名称: 2,6-二氨基-3,5-二氢-7-(3-噻吩基甲基)-4H-吡咯并(3,2-d)嘧啶-4-酮盐酸盐
• 英文名称: 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride
• 英文别名: 4H-Pyrrolo(3,2-d)pyrimidin-4-one, 2,6-diamino-1,5-dihydro-7-(3-thienylmethyl)-, monohydrochloride；2,6-diamino-7-(thiophen-3-ylmethyl)-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one;hydrochloride
• CAS: 115787-68-3
• 化学式: C₁₁H₁₁N₅OS*ClH
• 分子量: 297.768
• InChiKey: SLNICZJKQXPOJA-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.49
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  138
• 氢给体数：
  5
• 氢受体数：
  4

制备方法与用途

生物活性

CI 972 anhydrous 是一种有效的、具有口服活性的、竞争性的嘌呤核苷磷酸化酶 (PNP) 抑制剂（Ki=0.83 μM），正在开发作为 T 细胞选择性免疫抑制剂。

靶点

• Ki: 0.83 μM (PNP)

体内研究

CI 972 anhydrous (5-150 mg/kg; p.o.) 在大鼠中的给药一小时后，剂量依赖性地提高了血浆肌苷的水平。

反应信息

• 作为反应物：
  描述：

  2,6-二氨基-3,5-二氢-7-(3-噻吩基甲基)-4H-吡咯并(3,2-d)嘧啶-4-酮盐酸盐 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 生成 2-amino-4,5-dihydro-4-oxo-7-(thien-3-ylmethyl)-3H-pyrrolo[3,2-d]pyrimidine-6-diazonium chloride
  参考文献：
  名称：

  Process for the synthesis of

  摘要：

  本文描述了一种改进的方法，用于制备2-氨基-3,5-二氢-7-取代-4H-吡咯并[3,2-d]嘧啶-4-酮，其中2,6-二氨基-3,5-二氢-7-取代-4H-吡咯并[3,2-d]嘧啶-4-酮被转化为重氮盐，随后通过催化氢化反应得到所需的化合物，以及在该过程中使用的有价值的中间体。

  公开号：

  US05386031A1
• 作为产物：
  描述：

  2-(2-氨基-5-硝基-6-羰基-1,6-二氢嘧啶-4-YL)-3-(3-噻嗯基)丙腈 在 5%-palladium/activated carbon 、 氢气 、 potassium carbonate 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 15.0~35.0 ℃ 、446.08 kPa 条件下， 反应 5.0h， 以60%的产率得到2,6-二氨基-3,5-二氢-7-(3-噻吩基甲基)-4H-吡咯并(3,2-d)嘧啶-4-酮盐酸盐
  参考文献：
  名称：

  The Chemical Development of CI-972 and CI-1000:  A Continuous Nitration, A MgCl₂/Et₃N-Mediated C-Alkylation of a Chloronitropyrimidine, A Catalytic Protodediazotization of a Diazonium Salt, and an Air Oxidation of an Amine

  摘要：

  Efficient, large-scale processes were developed for the preparation of the potent PNP inhibitors 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (1) and 2-amino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (2), We report (1) a safe, continuous nitration process for the preparation of 2-amino-6-chloro-5-nitro-4-pyrimidinol (8a) and its stable diisopropylamine salt (8b), (2) the first MgCl2/ Et3N-mediated C-alkylation of a chloronitropyrimidine, (3) a rare catalytic protodediazotization of the diazonium salt 2-amino-4-oxo-7-thiophen-3-ylmethyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-6-diazonium chloride (14), (4) a single-step process to prepare 2 directly from 2-amino-6-hydroxy-5-nitro-alpha-(3-thienylmethyl)-4-pyrimidineacetonitrile (12) using a sponge nickel-catalyzed reduction, and (5) a method to convert the over-reduction by-product 2,5-diamino-6-(1-aminomethyl-2-thiophen-3-yl-ethyl)-pyrimidin-4-ol (16) into 2 using air oxidation.

  DOI：

  10.1021/op000298d

文献信息

• Process for the synthesis of
  申请人：Warner-Lambert Company

  公开号：US05386031A1

  公开（公告）日：1995-01-31

  An improved process for the preparation of 2-amino-3,5-dihydro-7-substituted-4H-pyrrolo[3,2-d]pyrimidin-4-ones is described wherein 2,6-diamino-3,5-dihydro-7-substituted-4H-pyrrolo[3,2-d]pyrimidin-4-one is converted to a diazonium salt which is subsequently catalytically hydrogenated to the desired compound, as well as valuable intermediates used in the process.

  本文描述了一种改进的方法，用于制备2-氨基-3,5-二氢-7-取代-4H-吡咯并[3,2-d]嘧啶-4-酮，其中2,6-二氨基-3,5-二氢-7-取代-4H-吡咯并[3,2-d]嘧啶-4-酮被转化为重氮盐，随后通过催化氢化反应得到所需的化合物，以及在该过程中使用的有价值的中间体。
• The Chemical Development of CI-972 and CI-1000:  A Continuous Nitration, A MgCl₂/Et₃N-Mediated C-Alkylation of a Chloronitropyrimidine, A Catalytic Protodediazotization of a Diazonium Salt, and an Air Oxidation of an Amine
  作者：Randall L. De Jong、James G. Davidson、Gary J. Dozeman、Philip J. Fiore、Punam Giri、Margaret E. Kelly、Timothy P. Puls、Ronald E. Seamans

  DOI：10.1021/op000298d

  日期：2001.5.1

  Efficient, large-scale processes were developed for the preparation of the potent PNP inhibitors 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (1) and 2-amino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (2), We report (1) a safe, continuous nitration process for the preparation of 2-amino-6-chloro-5-nitro-4-pyrimidinol (8a) and its stable diisopropylamine salt (8b), (2) the first MgCl2/ Et3N-mediated C-alkylation of a chloronitropyrimidine, (3) a rare catalytic protodediazotization of the diazonium salt 2-amino-4-oxo-7-thiophen-3-ylmethyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-6-diazonium chloride (14), (4) a single-step process to prepare 2 directly from 2-amino-6-hydroxy-5-nitro-alpha-(3-thienylmethyl)-4-pyrimidineacetonitrile (12) using a sponge nickel-catalyzed reduction, and (5) a method to convert the over-reduction by-product 2,5-diamino-6-(1-aminomethyl-2-thiophen-3-yl-ethyl)-pyrimidin-4-ol (16) into 2 using air oxidation.