7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methylbenzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic acid ethyl ester | 1260620-85-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methylbenzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic acid ethyl ester
• CAS: 1260620-85-6
• 化学式: C₃₀H₃₈FN₃O₅
• 分子量: 539.647
• InChiKey: PTGRQINFRWUZCD-JWQCQUIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  113.68
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methylbenzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic acid ethyl ester 在 sodium hydroxide 、 溶剂黄146 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 5.0h， 以96%的产率得到sodium 7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methylbenzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoate
  参考文献：
  名称：

  Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor

  摘要：

  Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 (1) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in which the yield was improved from 37% to 73%, a Suzuki/ozonolysis pathway that streamlined the downstream chemistry, and a reversed Wittig olefination strategy that improved the key coupling step from 50% to 95% yield. Multiple process hazards and most chromatography steps were removed, and a highly effective active pharmaceutical ingredient (API) salt formation, purification, and isolation protocol was also developed.

  DOI：

  10.1021/op100268e
• 作为产物：
  描述：

  1-(4-fluorophenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid 在 diethylmethoxyborane 、 palladium 10% on activated carbon 、 氢氟酸 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， -78.0~90.0 ℃ 、344.75 kPa 条件下， 反应 76.5h， 生成 7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methylbenzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic acid ethyl ester
  参考文献：
  名称：

  Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor

  摘要：

  Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 (1) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in which the yield was improved from 37% to 73%, a Suzuki/ozonolysis pathway that streamlined the downstream chemistry, and a reversed Wittig olefination strategy that improved the key coupling step from 50% to 95% yield. Multiple process hazards and most chromatography steps were removed, and a highly effective active pharmaceutical ingredient (API) salt formation, purification, and isolation protocol was also developed.

  DOI：

  10.1021/op100268e