(1S,3S,4R)-2-((1R)-1-苯基乙基)-2-氮杂双环[2.2.1]庚-5-烯-3-羧酸甲酯 | 130194-96-6

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (1S,3S,4R)-2-((1R)-1-苯基乙基)-2-氮杂双环[2.2.1]庚-5-烯-3-羧酸甲酯
• 英文名称: methyl (1S,3S,4R)-2-[(1R)-1-phenylethyl]-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate
• 英文别名: Methyl (1S,3S,4R)-2-((1R)-1-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate
• CAS: 130194-96-6
• 化学式: C₁₆H₁₉NO₂
• 分子量: 257.332
• InChiKey: PWUWUKQPSOGOPL-BEAPCOKYSA-N

物化性质

• 沸点：
  340.9±30.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (1S,3S,4R)-2-((1R)-1-苯基乙基)-2-氮杂双环[2.2.1]庚-5-烯-3-羧酸甲酯 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以63.8%的产率得到(2S)-环戊基甘氨酸甲酯
  参考文献：
  名称：

  Aza-Diels−Alder Reaction of Methyl 2-[(R)-1-Phenylethyl]iminoethanoate with Cyclopentadiene Using Practical and Environmentally Friendly Biphasic Solvent System

  摘要：

  Aza-Diels-Aider reaction between 2-[(R)-1-phenylethyl]imino-ethanoate (1) and cyclopentadiene using the biphasic solvent system (TMSCI-CH3OH/toluene) gave (1S,3S,4R)-2[(R)-1-phenylethyl]-2-aza-bicyclo[2.2.1]hept-5-ene-3-carboxylates (3a) in 32% isolated yield. The present method is advantageous for the large-scale synthesis, because (i) the reported methods required harmful and expensive fluorinated chemicals, (ii) methyl analogue 3a was practically isolated as a crystalline solid, and (iii) the reaction was conducted with very little observable exotherm. In addition, the absolute configurations of the other three diastereomers 2, 4, and 5 were unambiguously determined.

  DOI：

  10.1021/op049828m
• 作为产物：
  描述：

  [(E)-(S)-1-Phenyl-ethylimino]-acetic acid methyl ester 在 三氟化硼乙醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 (1S,3S,4R)-2-((1R)-1-苯基乙基)-2-氮杂双环[2.2.1]庚-5-烯-3-羧酸甲酯
  参考文献：
  名称：

  Asymmetric aza-diels-alder reaction using the chiral 1-phenyl ethyl imine of methyl glyoxylate

  摘要：

  DOI：

  10.1016/0040-4039(90)80136-a

文献信息

• [EN] 2-AZA-BICYCLO[2.2.1]HEPTANE DERIVATIVES<br/>[FR] DÉRIVÉS DE 2-AZA-BICYCLO[2.2.1]HEPTANE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009104155A1

  公开（公告）日：2009-08-27

  The invention relates to novel 2-aza-bicyclo[2.2.1]heptane derivatives of formula (I), wherein A, B, n and R1 are as described in the description, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.

  这项发明涉及公式（I）中的新型2-aza-双环[2.2.1]庚烷衍生物，其中A、B、n和R1如描述中所述，并且涉及将这类化合物或这类化合物的药用盐用作药物，特别是用作促觉醒素受体拮抗剂。
• [EN] MACROCYCLIC INHIBITORS OF PEPTIDYLARGININE DEIMINASES<br/>[FR] INHIBITEURS MACROCYCLIQUES DE PEPTIDYLARGININE DÉIMINASES
  申请人：GILEAD SCIENCES INC

  公开号：WO2021222353A1

  公开（公告）日：2021-11-04

  The present disclosure relates to novel compounds for use in therapeutic treatement of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

  本公开涉及用于治疗与肽精氨酸脱亚氨酶（PADs）相关的疾病的新化合物，例如肽精氨酸脱亚氨酶类型4（PAD4）。本公开还涉及用于制备这些化合物的过程和中间体，使用这些化合物的方法以及包含所述化合物的药物组合物。
• [EN] POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE<br/>[FR] COMPOSÉS DE CARBAMOYLPYRIDONE POLYCYCLIQUES ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：GILEAD SCIENCES INC

  公开号：WO2014100323A1

  公开（公告）日：2014-06-26

  Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, X, W, Y1, Y2, Ζ1 and Z4 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  披露了用于治疗人类免疫缺陷病毒（HIV）感染的化合物。这些化合物具有以下式（I）：包括立体异构体和其药用可接受的盐，其中R1、X、W、Y1、Y2、Ζ1和Z4如本文所定义。还披露了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。
• [EN] POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR USE FOR THE TREATMENT OF HIV INFECTIONS<br/>[FR] COMPOSÉS DE CARBAMOYLPYRIDONE POLYCYCLIQUE ET LEUR UTILISATION POUR LE TRAITEMENT DES INFECTIONS À VIH
  申请人：GILEAD SCIENCES INC

  公开号：WO2015006731A1

  公开（公告）日：2015-01-15

  Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, X, Y1, Y2, or L are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  用于治疗人类免疫缺陷病毒（HIV）感染的化合物被披露。这些化合物具有以下通式（I）：包括立体异构体及其药学上可接受的盐，其中R1、X、Y1、Y2或L如本文所定义。还披露了与这些化合物的制备和使用相关的方法，以及包含这些化合物的药物组合物。
• Enantioselective epoxidation of α,β-enones promoted by (1R,3S,4S)-2-azanorbornyl-3-methanol as an organocatalyst
  作者：Jun Lu、Yun-He Xu、Feng Liu、Teck-Peng Loh

  DOI：10.1016/j.tetlet.2008.07.175

  日期：2008.10

  (1R,3S,4S)-2-Azanorbornyl-3-methanol was synthesized form (R)-1-phenylethylamine and used as a catalyst for the enantioselective epoxidation of α,β-enones to afford the corresponding epoxides in good yields and high enantioselectivities at room temperature.

  （R）-1-苯基乙胺合成了（1 R，3 S，4 S）-2-氮杂降冰片基-3-甲醇，用作α，β-烯酮的对映选择性环氧化的催化剂，可得到良好的相应环氧化物在室温下收率和高对映选择性。