1,1-dimethylethyl [1-[4-(cyanoacetyl)phenyl]-1-methylethyl]carbamate | 314268-44-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,1-dimethylethyl [1-[4-(cyanoacetyl)phenyl]-1-methylethyl]carbamate
• 英文别名: tert-butyl N-{1-[4-(2-cyanoacetyl)phenyl]-1-methylethyl}carbamate；tert-butyl N-[2-[4-(2-cyanoacetyl)phenyl]propan-2-yl]carbamate
• CAS: 314268-44-5
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: BTIDPORWFSSDDG-UHFFFAOYSA-N

物化性质

• 沸点：
  487.4±40.0 °C(Predicted)
• 密度：
  1.095±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl [1-[4-(cyanoacetyl)phenyl]-1-methylethyl]carbamate 在 碳酸氢钠 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[4-(1-Amino-1-methylethyl)phenyl]-5-cyano-N-{4-[2-(2-ethylimidazol-1-yl)ethyl]phenyl}pyrimidine-2-amine
  参考文献：
  名称：

  4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: Synthesis and biological evaluation

  摘要：

  A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.021
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 sodium hydroxide 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 1,1-dimethylethyl [1-[4-(cyanoacetyl)phenyl]-1-methylethyl]carbamate
  参考文献：
  名称：

  4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: Synthesis and biological evaluation

  摘要：

  A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.021

文献信息

• 5-cyano-2-aminopyrimidine derivatives
  申请人：——

  公开号：US20020147339A1

  公开（公告）日：2002-10-10

  Pyrimidines of formula (1) are described 1 wherein Ar is an optionally substituted aromatic or heteroaromatic group; R 1 is a hydrogen atom or a straight or branched chain alkyl group; R 2 is a —X 1 —R 3 group where X 1 is a direct bond or a linker atom or group, and R 3 is an optionally substituted aliphatic, cycloaliphatic, heteroaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are selective KDR Kinase and/or FGFr Kinase inhibitors and are of use in the prophylaxis and treatment of disease states associated with angiogenesis.

  公式（1）中描述了嘧啶类化合物，其中Ar是可选择取代的芳香或杂芳基团；R1是氢原子或直链或支链烷基基团；R2是一个—X1—R3基团，其中X1是直接键或连接原子或基团，而R3是可选择取代的脂肪、环脂肪、杂原子脂肪、杂环脂肪、芳香或杂芳基团；以及它们的盐、溶剂合物、水合物和N-氧化物。这些化合物是选择性的KDR激酶和/或FGFr激酶抑制剂，并可用于预防和治疗与血管生成相关的疾病状态。
• Scalable Synthesis of the VEGF-R2 Kinase Inhibitor JNJ-17029259 Using Ultrasound-Mediated Addition of MeLi−CeCl₃ to a Nitrile
  作者：Michael Reuman、Sandra Beish、Jeremy Davis、Mark J. Batchelor、Martin C. Hutchings、David F. C. Moffat、Peter J. Connolly、Ronald K. Russell

  DOI：10.1021/jo7021372

  日期：2008.2.1

  [GRAPHICS]The preparation of the selective VEGF-R2 kinase inhibitor 10 (JNJ-17029259) is described in which the key precursor, 4-(5-isoxazolyl)benzonitrile, undergoes clean transformation to the corresponding cumylamine derivative with CeCL3-MeLi in THF. This high-yielding cerium mediated transformation is robust, reproducible, and readily scalable based on a requirement for the anhydrous CeCl3 to be milled and subjected to ultrasound treatment prior to addition of methyllithium.
• 4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: Synthesis and biological evaluation
  作者：Terry V. Hughes、Stuart L. Emanuel、Amanda K. Beck、Steven K. Wetter、Peter J. Connolly、Prabha Karnachi、Michael Reuman、Jabed Seraj、Angel R. Fuentes-Pesquera、Robert H. Gruninger、Steven A. Middleton、Ronghui Lin、Jeremy M. Davis、David F.C. Moffat

  DOI：10.1016/j.bmcl.2007.04.021

  日期：2007.6

  A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization. (c) 2007 Elsevier Ltd. All rights reserved.