tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate | 1460033-73-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate
• 英文别名: 4-(3-bromo-5-chloro-benzyl)piperazine-1-carboxylic acid tert-butyl ester；Tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate；tert-butyl 4-[(3-bromo-5-chlorophenyl)methyl]piperazine-1-carboxylate
• CAS: 1460033-73-1
• 化学式: C₁₆H₂₂BrClN₂O₂
• 分子量: 389.72
• InChiKey: OPAUQHSGNSLJPK-UHFFFAOYSA-N

物化性质

• 沸点：
  431.3±45.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate 在 2-二叔丁基膦-3,4,5,6-四甲基-2′,4′,6′-三异丙基-1,1′-联苯 、 盐酸 、 potassium phosphate 、 palladium diacetate 、 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 64.0h， 生成 4-[3-chloro-5-(4-chlorophenoxy)benzyl]piperazine-1-carboxylic acid pyridin-3-ylamide hydrochloride
  参考文献：
  名称：

  The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors

  摘要：

  The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4: 1 to as low as 0.02: 1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold. It was not possible to predict the degree of central nervous system (CNS) penetration from the volumes of distribution (V-d) obtained from pharmacokinetic (PK) experiments as very high V(d)s did not correlate with high B/P ratios. Similarly, calculated topological polar surface areas (TPSAs) did not consistently correlate with the degree of brain penetration. The lowest B/P ratios were observed for those compounds that were significantly ionized at physiological pH. However, as this class of compounds inhibits the FAAH enzyme through covalent modification, low B/P ratios did not preclude effective central target engagement. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.05.001
• 作为产物：
  描述：

  3-溴-5-氯苯甲醛 、 N-Boc-哌嗪 在 tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate 作用下， 以to provide tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate as an amorphous white solid (1.2 g, 56% yield)的产率得到tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate
  参考文献：
  名称：

  CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME

  摘要：

  本文提供了一些氨基甲酸酯化合物，可能对例如疼痛、实体肿瘤和/或肥胖症的治疗有用。

  公开号：

  US20150080364A1
• 作为试剂：
  描述：

  3-溴-5-氯苯甲醛 、 N-Boc-哌嗪 在 tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate 作用下， 以to provide tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate as an amorphous white solid (1.2 g, 56% yield)的产率得到tert-butyl 4-(3-bromo-5-chlorobenzyl)piperazine-1-carboxylate
  参考文献：
  名称：

  CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME

  摘要：

  本文提供了一些氨基甲酸酯化合物，可能对例如疼痛、实体肿瘤和/或肥胖症的治疗有用。

  公开号：

  US20150080364A1

文献信息

• [EN] CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME<br/>[FR] COMPOSÉS CARBAMATES ET LEUR PROCÉDÉ DE FABRICATION ET D'UTILISATION
  申请人：ABIDE THERAPEUTICS

  公开号：WO2013142307A1

  公开（公告）日：2013-09-26

  Provided herein are carbamate compounds which may be useful in the treatment of, for example, pain, solid tumors and/or obesity.

  本文提供的是可能在治疗疼痛、实体肿瘤和/或肥胖等方面有用的氨基甲酸酯化合物。
• US9567302B2
  申请人：——

  公开号：US9567302B2

  公开（公告）日：2017-02-14
• The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors
  作者：John M. Keith、Mark S. Tichenor、Richard L. Apodaca、Wei Xiao、William M. Jones、Mark Seierstad、Joan M. Pierce、James A. Palmer、Michael Webb、Mark J. Karbarz、Brian P. Scott、Sandy J. Wilson、Michelle L. Wennerholm、Michele Rizzolio、Raymond Rynberg、Sandra R. Chaplan、J. Guy Breitenbucher

  DOI：10.1016/j.bmcl.2016.05.001

  日期：2016.7

  The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4: 1 to as low as 0.02: 1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold. It was not possible to predict the degree of central nervous system (CNS) penetration from the volumes of distribution (V-d) obtained from pharmacokinetic (PK) experiments as very high V(d)s did not correlate with high B/P ratios. Similarly, calculated topological polar surface areas (TPSAs) did not consistently correlate with the degree of brain penetration. The lowest B/P ratios were observed for those compounds that were significantly ionized at physiological pH. However, as this class of compounds inhibits the FAAH enzyme through covalent modification, low B/P ratios did not preclude effective central target engagement. (C) 2016 Elsevier Ltd. All rights reserved.
• CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME
  申请人：Abide Therapeutics, Inc.

  公开号：US20150080364A1

  公开（公告）日：2015-03-19

  Provided herein are carbamate compounds which may be useful in the treatment of for example, pain, solid tumors and/or obesity.

  本文提供了一些氨基甲酸酯化合物，可能对例如疼痛、实体肿瘤和/或肥胖症的治疗有用。