2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(1H)-one | 1307381-60-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(1H)-one
• 英文别名: 2-(tert-Butyl)-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one；2-tert-butylspiro[4,6-dihydroindazole-5,4'-piperidine]-7-one
• CAS: 1307381-60-7
• 化学式: C₁₅H₂₃N₃O
• 分子量: 261.367
• InChiKey: LLYSHKYHTJEQDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(1H)-one 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以75.3 g的产率得到2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(1H)-one hydrochloride
  参考文献：
  名称：

  Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors

  摘要：

  Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.

  DOI：

  10.1021/jo202377g
• 作为产物：
  描述：

  benzyl 2-tert-butyl-7-oxo-2,4,6,7-tetrahydrospiro[indazole-5,4'-piperidine]-1'-carboxylate 在 1-甲基-1,4-环己二烯 、 20% palladium hydroxide on charcoal 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 生成 2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(1H)-one
  参考文献：
  名称：

  Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors

  摘要：

  Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.

  DOI：

  10.1021/jo202377g

文献信息

• SUBSTITUTED ACETYL-COA CARBOXYLASE INHIBITORS
  申请人：Dow Robert Lee

  公开号：US20120270893A1

  公开（公告）日：2012-10-25

  The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R 1 , R 2 and R 3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.

  该发明提供了公式（I）的化合物或其药用可接受的盐；其中G为R1，R2和R3如本文所述；其药用组合物；以及其在治疗由于抑制动物中乙酰辅酶A羧化酶而调节的疾病、症状或疾病中的用途。
• N2-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
  申请人：Bagley Scott William

  公开号：US20120225900A1

  公开（公告）日：2012-09-06

  The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of said compound, wherein R 1 , R 2 , R 3 and R 4 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.

  本发明提供了式(I)的化合物或其药学上可接受的盐，其中R1、R2、R3和R4如本文所述；其药物组合物；以及在治疗动物中通过抑制乙酰辅酶A羧化酶酶的作用调节的疾病、症状或疾患中使用该化合物的方法。
• US8802688B2
  申请人：——

  公开号：US8802688B2

  公开（公告）日：2014-08-12
• Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors
  作者：Scott W. Bagley、James A. Southers、Shawn Cabral、Colin R. Rose、David J. Bernhardson、David J. Edmonds、Jana Polivkova、Xiaojing Yang、Daniel W. Kung、David A. Griffith、Scott J. Bader

  DOI：10.1021/jo202377g

  日期：2012.2.3

  Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.