7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid ethyl ester | 1260620-83-4

• 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-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid ethyl ester
• CAS: 1260620-83-4
• 化学式: C₃₀H₃₄FN₃O₅
• 分子量: 535.615
• InChiKey: WAFHSRCCLSGVBT-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.66
• 重原子数：
  39.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110.52
• 氢给体数：
  2.0
• 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-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid ethyl ester 在 diethylmethoxyborane 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以96%的产率得到7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methylbenzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-hept-6-enoic 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
• 作为产物：
  描述：

  1-(4-fluorophenyl)-5-formyl-4-isopropyl-1H-pyrazole-3-carboxylic acid 在 氢氟酸 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 71.5h， 生成 7-[2-(4-fluorophenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic 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