4-chloro-6-{4-[(R)-1-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-pyrimidine | 1020064-27-0

• 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: 4-chloro-6-{4-[(R)-1-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-pyrimidine
• 英文别名: 4-chloro-6-[4-[(1R)-1-(4-fluorophenyl)ethyl]piperazin-1-yl]pyrimidine
• CAS: 1020064-27-0
• 化学式: C₁₆H₁₈ClFN₄
• 分子量: 320.797
• InChiKey: HJEZIASIODMWPT-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-1-(1-(4-氟苯基)乙基)哌嗪 、 4,6-二氯嘧啶 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以100%的产率得到4-chloro-6-{4-[(R)-1-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-pyrimidine
  参考文献：
  名称：

  Practical Synthesis of a Vanilloid Receptor-1 Antagonist

  摘要：

  Small molecule TRPV1 antagonists have been a recent focus in the search for pain treatment agents. We herein describe a practical and scalable synthesis of AMG 628 (1), a bis-substituted pyrimidine derivative that was identified as a highly efficacious agent, suitable for clinical development. Highlights of our approach include a practical route to a substituted benzothiazole, a scalable synthesis of an enantiopure piperazine fragment, and identification of conditions for selective coupling reactions on 2,6-dichloropyrimidine, to access the active pharmaceutical ingredient in high purity and overall yield.

  DOI：

  10.1021/jo8002216

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Wang Hui-Ling

  公开号：US20050176726A1

  公开（公告）日：2005-08-11

  Pyrimidine ethers and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  嘌呤醚及含有它们的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、伴有炎症成分的皮肤问题、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧灼性疼痛、交感神经维持性疼痛、感觉缺失综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿生殖、胃肠或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道紊乱、胃溃疡、十二指肠溃疡、腹泻、由坏死剂引起的胃损伤、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• US7511044B2
  申请人：——

  公开号：US7511044B2

  公开（公告）日：2009-03-31
• Practical Synthesis of a Vanilloid Receptor-1 Antagonist
  作者：Oliver R. Thiel、Charles Bernard、Tony King、Mina Dilmeghani-Seran、Tracy Bostick、Robert D. Larsen、Margaret M. Faul

  DOI：10.1021/jo8002216

  日期：2008.5.1

  Small molecule TRPV1 antagonists have been a recent focus in the search for pain treatment agents. We herein describe a practical and scalable synthesis of AMG 628 (1), a bis-substituted pyrimidine derivative that was identified as a highly efficacious agent, suitable for clinical development. Highlights of our approach include a practical route to a substituted benzothiazole, a scalable synthesis of an enantiopure piperazine fragment, and identification of conditions for selective coupling reactions on 2,6-dichloropyrimidine, to access the active pharmaceutical ingredient in high purity and overall yield.