ethyl 2-(5-chloro-2-methylbenzoyl)-3-(dimethylamino)acrylate | 1224944-52-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 2-(5-chloro-2-methylbenzoyl)-3-(dimethylamino)acrylate
• 英文别名: Ethyl 2-(5-chloro-2-methylbenzoyl)-3-(dimethylamino)acrylate；ethyl 2-(5-chloro-2-methylbenzoyl)-3-(dimethylamino)prop-2-enoate
• CAS: 1224944-52-8
• 化学式: C₁₅H₁₈ClNO₃
• 分子量: 295.766
• InChiKey: FGBRQOYJYBPAFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(5-chloro-2-methylbenzoyl)-3-(dimethylamino)acrylate 在 氨 、 caesium carbonate 、 N,N-二异丙基乙胺 、 肼 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 30.0h， 生成 5-amino-N-(3-(5-chloro-2-methylphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors

  摘要：

  The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in disc-ova-ring selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibit-or of Jak2. Optimization of lead compounds 7a-b and 8 in this chemical series for activity against Jak2, selectivity against other Jak family kinases, and good in vivo pharmacokinetic properties led to the discovery of 7j. In a SET2 xenograft model that is dependent on Jak2 for growth, 7j demonstrated a time-dependent knock-down of pSTAT5, a downstream target of Jak2.

  DOI：

  10.1021/jm3012239
• 作为产物：
  描述：

  5-氯-2-甲基苯甲酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 30.0h， 生成 ethyl 2-(5-chloro-2-methylbenzoyl)-3-(dimethylamino)acrylate
  参考文献：
  名称：

  用于喹诺酮支架合成的无金属高价碘促进串联羰基迁移和未活化的 C(Ph)–C(Alkyl) 键断裂

  摘要：

  描述了一种出人意料的碘（III）介导的 3-（甲基氨基）-2-（2-取代苯甲酰基）丙烯酸酯的 C（sp 3）-C（sp 2）键断裂，用于有效合成特权支架 4-喹诺酮类药物。值得注意的是，广泛的烷基（例如甲基、叔丁基或烷基链）可以在该系统中方便地裂解。详细的机制研究表明，转化通过级联同环化和 1,2-羰基迁移进行，较小的键能通过烯胺自由基中间体决定邻位C-C 键断裂而不是 C-H 键断裂。

  DOI：

  10.1039/d2cc02245a

文献信息

• [EN] PYRAZOLOPYRIMIDINE JAK INHIBITOR COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS INHIBITEURS DE JAK À LA PYRAZOLOPYRIMIDINE ET PROCÉDÉS
  申请人：GENENTECH INC

  公开号：WO2010051549A1

  公开（公告）日：2010-05-06

  The invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient. Ia

  这项发明提供了Formula Ia的JAK激酶抑制剂，其对映体、二对映体或其药学上可接受的盐，其中R1、R2、R7和Z在此处被定义，包括Formula Ia化合物和药学上可接受的载体、辅料或载体的药物组合物，以及治疗或减轻对JAK激酶活性抑制有响应的疾病或病况的方法。
• PYRAZOLOPYRIMIDINE JAK INHIBITOR COMPOUNDS AND METHODS
  申请人：Blaney Jeffrey

  公开号：US20120022043A1

  公开（公告）日：2012-01-26

  The invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient.

  该发明提供了Formula Ia的JAK激酶抑制剂，其对映体、二对映体或其药学上可接受的盐，其中R1、R2、R7和Z在此处定义，包括Formula Ia化合物和药学上可接受的载体、辅料或载体的药物组合物，以及治疗或减轻对JAK激酶活性抑制有响应的疾病或病况的方法。
• Pyrazolopyrimidine JAK inhibitor compounds and methods
  申请人：Blaney Jeffrey

  公开号：US08637526B2

  公开（公告）日：2014-01-28

  The invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient.

  该发明提供了Formula Ia的JAK激酶抑制剂、对映体、对映异构体或其药学上可接受的盐，其中R1、R2、R7和Z在此定义，以及包括Formula Ia化合物和药学上可接受的载体、辅料或载体的制药组合物，以及治疗或减轻患者对JAK激酶活性抑制响应的疾病或病情的方法。
• Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors
  作者：Emily J. Hanan、Anne van Abbema、Kathy Barrett、Wade S. Blair、Jeff Blaney、Christine Chang、Charles Eigenbrot、Sean Flynn、Paul Gibbons、Christopher A. Hurley、Jane R. Kenny、Janusz Kulagowski、Leslie Lee、Steven R. Magnuson、Claire Morris、Jeremy Murray、Richard M. Pastor、Tom Rawson、Michael Siu、Mark Ultsch、Aihe Zhou、Deepak Sampath、Joseph P. Lyssikatos

  DOI：10.1021/jm3012239

  日期：2012.11.26

  The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in disc-ova-ring selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibit-or of Jak2. Optimization of lead compounds 7a-b and 8 in this chemical series for activity against Jak2, selectivity against other Jak family kinases, and good in vivo pharmacokinetic properties led to the discovery of 7j. In a SET2 xenograft model that is dependent on Jak2 for growth, 7j demonstrated a time-dependent knock-down of pSTAT5, a downstream target of Jak2.
• Metal-free hypervalent iodine-promoted tandem carbonyl migration and unactivated C(Ph)–C(Alkyl) bond cleavage for quinolone scaffold synthesis
  作者：Li-Rui Song、He Li、Shen-Feng Wang、Jian-Ping Lin、Bin Huang、Ya-Qiu Long

  DOI：10.1039/d2cc02245a

  日期：——

  An unexpected iodine(III)-mediated C(sp3)–C(sp2) bond cleavage of 3-(methylamino)-2-(2-substitutedbenzoyl)acrylates for efficient synthesis of privileged scaffold 4-quinolones was described. Notably, a wide range of alkyl groups (e.g. methyl, tert-butyl or alkyl chain) can be conveniently cleaved in this system. The detailed mechanism studies revealed that the transformation proceeded through cascade

  描述了一种出人意料的碘（III）介导的 3-（甲基氨基）-2-（2-取代苯甲酰基）丙烯酸酯的 C（sp 3）-C（sp 2）键断裂，用于有效合成特权支架 4-喹诺酮类药物。值得注意的是，广泛的烷基（例如甲基、叔丁基或烷基链）可以在该系统中方便地裂解。详细的机制研究表明，转化通过级联同环化和 1,2-羰基迁移进行，较小的键能通过烯胺自由基中间体决定邻位C-C 键断裂而不是 C-H 键断裂。