Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate | 930595-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate
• 英文别名: tert-butyl 3-[7-[bis(2-trimethylsilylethoxymethyl)amino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate
• CAS: 930595-70-3
• 化学式: C₂₈H₅₁N₅O₄Si₂
• 分子量: 577.915
• InChiKey: LDSQZIPTFQEXGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.27
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate 在 N-碘代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 以92%的产率得到Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  CHK1抑制剂MK-8776（SCH 900776）的收敛制剂

  摘要：

  这封信描述了向CHK1抑制剂MK-8776汇聚，高效途径的发展。该合成方法依赖于双吡唑加合物10与光学纯的β-酮腈9的环化，以一步构建吡唑并[1，5- a ]嘧啶骨架。

  DOI：

  10.1016/j.tetlet.2016.04.102
• 作为产物：
  描述：

  3-(3-甲氧基-3-氧代丙酰基)哌啶-1-羧酸叔丁酯 在 氨 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基苯胺 、 异丙醇 、 甲苯 为溶剂， 生成 Tert-butyl 3-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  CHK1抑制剂MK-8776（SCH 900776）的收敛制剂

  摘要：

  这封信描述了向CHK1抑制剂MK-8776汇聚，高效途径的发展。该合成方法依赖于双吡唑加合物10与光学纯的β-酮腈9的环化，以一步构建吡唑并[1，5- a ]嘧啶骨架。

  DOI：

  10.1016/j.tetlet.2016.04.102

文献信息

• Methods for inhibiting protein kinases
  申请人：Guzi J. Timothy

  公开号：US20070082900A1

  公开（公告）日：2007-04-12

  The present invention provides methods for inhibiting protein kinases selected from the group consisting of AKT, Checkpoint kinase, Aurora kinase, Pim kinases, and tyrosine kinase using pyrazolo[1,5-a]pyrimidine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with protein kinases using such compounds.

  本发明提供了使用吡唑并[1,5-a]嘧啶化合物抑制选自AKT、检查点激酶、极光激酶、Pim激酶和酪氨酸激酶的蛋白激酶的方法，以及使用这些化合物治疗、预防、抑制或改善与蛋白激酶相关的一种或多种疾病的方法。
• Pyrazolopyrimidines as protein kinase inhibitors
  申请人：Paruch Kamil

  公开号：US20070083044A1

  公开（公告）日：2007-04-12

  In its many embodiments, the present invention provides a novel class of amino-substituted pyrazolo[1,5-a]pyrimidine compounds as inhibitors of protein and/or checkpoint kinases, methods of preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of preparing pharmaceutical formulations including one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the protein or checkpoint kinases using such compounds or pharmaceutical compositions.

  在本发明的多种实施方式中，提供了一类新颖的氨基取代的吡唑并[1,5-a]嘧啶化合物，作为蛋白质和/或检查点激酶的抑制剂，制备此类化合物的方法，包含一种或多种此类化合物的药物组合物，制备包含一种或多种此类化合物的药物制剂的方法，以及使用此类化合物或药物组合物治疗、预防、抑制或缓解与蛋白质或检查点激酶相关的一种或多种疾病的方法。
• Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach—Part 2
  作者：Marc Labroli、Kamil Paruch、Michael P. Dwyer、Carmen Alvarez、Kartik Keertikar、Cory Poker、Randall Rossman、Jose S. Duca、Thierry O. Fischmann、Vincent Madison、David Parry、Nicole Davis、Wolfgang Seghezzi、Derek Wiswell、Timothy J. Guzi

  DOI：10.1016/j.bmcl.2010.10.114

  日期：2011.1

  Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo [1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors. (c) 2010 Elsevier Ltd. All rights reserved.
• Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach—Part 1
  作者：Michael P. Dwyer、Kamil Paruch、Marc Labroli、Carmen Alvarez、Kerry M. Keertikar、Cory Poker、Randall Rossman、Thierry O. Fischmann、Jose S. Duca、Vincent Madison、David Parry、Nicole Davis、Wolfgang Seghezzi、Derek Wiswell、Timothy J. Guzi

  DOI：10.1016/j.bmcl.2010.10.113

  日期：2011.1

  The synthesis and hit-to-lead SAR development of a pyrazolo[1,5-a]pyrimidine hit 4 is described leading to a series of potent, selective CHK1 inhibitors such as compound 17r. In the Letter, the further utility of the pyrazolo[1,5-a]pyrimidine template for the development of potent, selective kinase inhibitors is detailed. (c) 2010 Elsevier Ltd. All rights reserved.
• A convergent preparation of the CHK1 inhibitor MK-8776 (SCH 900776)
  作者：Marc A. Labroli、Michael P. Dwyer、Cory Poker、Kerry M. Keertikar、Randall Rossman、Timothy J. Guzi

  DOI：10.1016/j.tetlet.2016.04.102

  日期：2016.6

  This Letter describes the development of a convergent, efficient route to the CHK1 inhibitor MK-8776. This synthetic approach relies upon the cyclization of a bispyrazole adduct 10 with a optically pure β-keto nitrile 9 to construct the pyrazolo[1,5-a]pyrimidine scaffold in a single step.

  这封信描述了向CHK1抑制剂MK-8776汇聚，高效途径的发展。该合成方法依赖于双吡唑加合物10与光学纯的β-酮腈9的环化，以一步构建吡唑并[1，5- a ]嘧啶骨架。