1-tert-butyl 3-methyl 4-{[(1R)-1-phenylethyl]amino}-5,6-dihydropyridine-1,3(2H)-dicarboxylate | 362489-59-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 1-tert-butyl 3-methyl 4-{[(1R)-1-phenylethyl]amino}-5,6-dihydropyridine-1,3(2H)-dicarboxylate
• 英文别名: (R)-4-(1-phenyl-ethylamino)-2,5-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester；4-((R)-1-phenyl-ethylamino)-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester；1-O-tert-butyl 5-O-methyl 4-[[(1R)-1-phenylethyl]amino]-3,6-dihydro-2H-pyridine-1,5-dicarboxylate
• CAS: 362489-59-6
• 化学式: C₂₀H₂₈N₂O₄
• 分子量: 360.453
• InChiKey: KRXJITHGLPLONE-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 3-methyl 4-{[(1R)-1-phenylethyl]amino}-5,6-dihydropyridine-1,3(2H)-dicarboxylate 在 sodium tetrahydroborate 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.0h， 以95%的产率得到1-tert-butyl 3-methyl (3S,4R)-4-{[(1R)-1-phenylethyl]-amino}piperidine-1,3-dicarboxylate
  参考文献：
  名称：

  Efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate, a useful intermediate for the synthesis of nociceptin antagonists

  摘要：

  An efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 1, a useful intermediate for the synthesis of nociceptin antagonists, has been developed. This method includes the following key steps: (1) diastereoseiective reduction of a chiral enaminoester 3 having (R)-1-phenylethylamine as a chiral pool constituent with the use of a combined TFA-NaBH4 reduction system and (2) efficient isomerization from 3,4-cis-substituted piperidine 8 to 3,4-trans-substituted piperidine 1 under basic conditions. The above methods proved to be applicable for large-scale operation and hundred grams of enantiomerically pure compound 1 (>98% ee) was obtained. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2009.07.046
• 作为产物：
  描述：

  R(+)-alpha-甲基苄胺 、 1-(tert-butyl) 3-methyl 4-oxopiperidine-1,3-dicarboxylate 在 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以58 g的产率得到1-tert-butyl 3-methyl 4-{[(1R)-1-phenylethyl]amino}-5,6-dihydropyridine-1,3(2H)-dicarboxylate
  参考文献：
  名称：

  Efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate, a useful intermediate for the synthesis of nociceptin antagonists

  摘要：

  An efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 1, a useful intermediate for the synthesis of nociceptin antagonists, has been developed. This method includes the following key steps: (1) diastereoseiective reduction of a chiral enaminoester 3 having (R)-1-phenylethylamine as a chiral pool constituent with the use of a combined TFA-NaBH4 reduction system and (2) efficient isomerization from 3,4-cis-substituted piperidine 8 to 3,4-trans-substituted piperidine 1 under basic conditions. The above methods proved to be applicable for large-scale operation and hundred grams of enantiomerically pure compound 1 (>98% ee) was obtained. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2009.07.046

文献信息

• Beta-sulfonamide hydroxamic acid inhibitors of tace/matrix metalloproteinase
  申请人：Levin I. Jeremy

  公开号：US20060211730A1

  公开（公告）日：2006-09-21

  This invention provides compounds of Formula I, having the structure: that are useful in treating diseases or disorders mediated by TNF-α, such as arthritis (rheumatoid arthritis (RA), juvenile RA, psoriatic arthritis, osteoarthritis etc), tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection, ankylosing spondylitis, psoriasis, sepsis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, asthma, idiopathic pulmonary fibrosis, vasculitis, systemic lupus erythematosus, irritable bowel syndrome, acute coronary syndrome, hepatitis C, cachexia, COPD, stroke or type 2 diabetes, and for alleviation of symptoms thereof. The invention further provides methods for use of the compounds.

  这项发明提供了具有结构的Formula I的化合物，这些化合物在治疗由TNF-α介导的疾病或紊乱方面非常有用，如关节炎（类风湿关节炎（RA），幼年RA，银屑病性关节炎，骨关节炎等），肿瘤转移，组织溃疡，异常伤口愈合，牙周病，骨病，糖尿病（胰岛素抵抗）和HIV感染，强直性脊柱炎，银屑病，败血症，多发性硬化，克罗恩病，退行性软骨丢失，哮喘，特发性肺纤维化，血管炎，系统性红斑狼疮，肠易激综合征，急性冠状动脉综合征，丙型肝炎，虚弱，慢性阻塞性肺病，中风或2型糖尿病的缓解症状。该发明还提供了使用这些化合物的方法。
• N-ureidoheterocycloalkyl-piperidines as modulators of chemokine receptor activity
  申请人：——

  公开号：US20030032654A1

  公开（公告）日：2003-02-13

  The present application describes modulators of CCR3 of formula (I): 1 or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3的调节剂，其化学公式为(I)： 1 或其药用可接受的盐形式，用于预防哮喘和其他过敏性疾患。
• US6627629B2
  申请人：——

  公开号：US6627629B2

  公开（公告）日：2003-09-30
• US6949546B2
  申请人：——

  公开号：US6949546B2

  公开（公告）日：2005-09-27
• Efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate, a useful intermediate for the synthesis of nociceptin antagonists
  作者：Hideki Jona、Jun Shibata、Masanori Asai、Yasuhiro Goto、Sachie Arai、Shigeru Nakajima、Osamu Okamoto、Hiroshi Kawamoto、Yoshikazu Iwasawa

  DOI：10.1016/j.tetasy.2009.07.046

  日期：2009.11

  An efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 1, a useful intermediate for the synthesis of nociceptin antagonists, has been developed. This method includes the following key steps: (1) diastereoseiective reduction of a chiral enaminoester 3 having (R)-1-phenylethylamine as a chiral pool constituent with the use of a combined TFA-NaBH4 reduction system and (2) efficient isomerization from 3,4-cis-substituted piperidine 8 to 3,4-trans-substituted piperidine 1 under basic conditions. The above methods proved to be applicable for large-scale operation and hundred grams of enantiomerically pure compound 1 (>98% ee) was obtained. (C) 2009 Published by Elsevier Ltd.