[5,6,7,8-tetrahydro-4-oxo-5-[2-(pyridin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carboxylic acid | 1026409-99-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [5,6,7,8-tetrahydro-4-oxo-5-[2-(pyridin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carboxylic acid
• 英文别名: 4-oxo-5-(2-pyridin-4-ylethyl)-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepine-2-carboxylic acid
• CAS: 1026409-99-3
• 化学式: C₁₅H₁₆N₄O₃
• 分子量: 300.317
• InChiKey: CHAMAGGGYHLSJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  88.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [5,6,7,8-tetrahydro-4-oxo-5-[2-(pyridin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carboxylic acid 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 水 、 乙腈 为溶剂， 70.0 ℃ 、689.47 kPa 条件下， 反应 30.0h， 生成 2(S)-[(p-toluenesulfonyl)amino]-3-[[[5,6,7,8-tetrahydro-4-oxo-5-[2-(pyridin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carbonyl]amino]propionic acid
  参考文献：
  名称：

  A Highly Convergent Synthesis of a Fibrinogen Receptor Antagonist

  摘要：

  A practical multikilogram synthesis of 2(S)-[(p-toluenesulfonyl)amino]-3-[[[5,6,7,8-tetrahydro-4-oxo-5-[2-(piperidin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carbonyl]amino]propionic acid pentahydrate (1), an oral fibrinogen receptor antagonist, is described. The nine-step convergent process, which afforded 1 in 37% overall yield, included pyrazole 5a and N-tosylaminoalanine 16 as key fragments. Pyrazole 5a was obtained from pyrazole-3,5-dicarboxylic acid by esterification with MeOH, alkylation/cyclization with 3-bromopropylamine, and Michael addition with 4-vinylpyridine. N-Tosylaminoalanine 16 was prepared by tosylation of asparagine, Hofmann reaction, and benzyl esterification. Saponification of pyrazole 5a, coupling of the acid with N-tosylaminoalanine 16, and Pd-catalyzed hydrogenolysis and pyridine reduction completed the synthesis.

  DOI：

  10.1021/jo990644t
• 作为产物：
  描述：

  4-氧代-4H,5H,6H,7H,8H-吡唑并[1,5-a][1,4]二氮杂-2-羧酸甲酯 在 sodium hydroxide 、 N-甲基吲哚酮 、 叔丁醇 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 [5,6,7,8-tetrahydro-4-oxo-5-[2-(pyridin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carboxylic acid
  参考文献：
  名称：

  A Highly Convergent Synthesis of a Fibrinogen Receptor Antagonist

  摘要：

  A practical multikilogram synthesis of 2(S)-[(p-toluenesulfonyl)amino]-3-[[[5,6,7,8-tetrahydro-4-oxo-5-[2-(piperidin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1,4]diazepin-2-yl]carbonyl]amino]propionic acid pentahydrate (1), an oral fibrinogen receptor antagonist, is described. The nine-step convergent process, which afforded 1 in 37% overall yield, included pyrazole 5a and N-tosylaminoalanine 16 as key fragments. Pyrazole 5a was obtained from pyrazole-3,5-dicarboxylic acid by esterification with MeOH, alkylation/cyclization with 3-bromopropylamine, and Michael addition with 4-vinylpyridine. N-Tosylaminoalanine 16 was prepared by tosylation of asparagine, Hofmann reaction, and benzyl esterification. Saponification of pyrazole 5a, coupling of the acid with N-tosylaminoalanine 16, and Pd-catalyzed hydrogenolysis and pyridine reduction completed the synthesis.

  DOI：

  10.1021/jo990644t