3-(4-氨基-2-氟苯基)吡咯烷-1-羧酸叔丁酯 | 1034497-93-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 3-(4-氨基-2-氟苯基)吡咯烷-1-羧酸叔丁酯
• 英文名称: 3-(4-amino-2-fluorophenyl)pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-Butyl 3-(4-amino-2-fluorophenyl)pyrrolidine-1-carboxylate；tert-butyl 3-(4-amino-2-fluorophenyl)pyrrolidine-1-carboxylate
• CAS: 1034497-93-2
• 化学式: C₁₅H₂₁FN₂O₂
• 分子量: 280.342
• InChiKey: AKCFUVAWGKJGIM-UHFFFAOYSA-N

物化性质

• 沸点：
  384.6±42.0 °C(Predicted)
• 密度：
  1.179±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴-3-氟苯胺 、 1-Boc-四氢吡咯 在 palladium diacetate 仲丁基锂 、 鹰爪豆碱 、 zinc(II) chloride 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 乙醚 为溶剂， 反应 17.5h， 生成 3-(4-氨基-2-氟苯基)吡咯烷-1-羧酸叔丁酯 、 (R)-2-(4-氨基-2-氟苯基)吡咯烷-1-羧酸叔丁酯 、 (S)-2-(4-amino-2-fluorophenyl)pyrrolidine-1-carboxylic acid tert-butyl ester 、 1-叔丁氧羰基-2,3-二氢吡咯
  参考文献：
  名称：

  Enantioselective Pd-Catalyzed α-Arylation of N-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator

  摘要：

  A short and practical synthesis of glucokinase activator I was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound I in a 31 % overall yield over-six steps.

  DOI：

  10.1021/jo8006804

文献信息

• 8-ETHYL-6-(ARYL)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES FOR THE TREATMENT OF NERVOUS SYSTEM DISORDERS AND CANCER
  申请人：Campbell David

  公开号：US20140163026A1

  公开（公告）日：2014-06-12

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders or neurofibromatosis. Also described herein are methods of utilizing PAK inhibitors for the treatment of cancer.

  本文提供了PAK抑制剂及其在治疗中枢神经系统疾病（如神经精神疾病或神经纤维瘤）方面的应用方法。本文还描述了利用PAK抑制剂治疗癌症的方法。
• Enantioselective Pd-Catalyzed α-Arylation of <i>N</i>-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator
  作者：Artis Klapars、Kevin R. Campos、Jacob H. Waldman、Daniel Zewge、Peter G. Dormer、Cheng-yi Chen

  DOI：10.1021/jo8006804

  日期：2008.7.1

  A short and practical synthesis of glucokinase activator I was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound I in a 31 % overall yield over-six steps.