(2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid | 210288-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid
• 英文别名: [(2S)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-yl]acetic acid；2-[(2S)-4-methyl-3-oxo-2,5-dihydro-1H-1,4-benzodiazepin-2-yl]acetic acid
• CAS: 210288-68-9
• 化学式: C₁₂H₁₄N₂O₃
• 分子量: 234.255
• InChiKey: CLWDLBDPVUWYEW-JTQLQIEISA-N

物化性质

• 沸点：
  525.4±43.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid 以37.5% over 2 steps的产率得到2-(7-iodo-4-methyl-3-oxo-2,5-dihydro-1H-1,4-benzodiazepin-2-yl)acetic acid
  参考文献：
  名称：

  Org. Process Res. Dev. 2003, 7, 663-675

  摘要：

  DOI：
• 作为产物：
  描述：

  3-methyl-2-methoxycarbonyl-2-(methoxycarbonylmethyl)-1,2,3,4-tetrahydroquinazoline 在 palladium on activated charcoal Candida antarctica lipase B 、 氨 、 氢气 、 sodium methylate 、 叔丁醇 作用下， 以 甲醇 、 水 为溶剂， 50.0~65.0 ℃ 、413.68 kPa 条件下， 生成 (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid
  参考文献：
  名称：

  A new synthesis of the GPIIb/IIIa receptor antagonist SB-214857-A

  摘要：

  A new synthesis of lotrafiban SB-214857-A is reported. The key steps are the preparation of racemic (4-melhyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c][1,4]diazepin-2-yl)-acid methyl ester from 2-nitrobenzyl alcohol, a resolution using an immobilised lipase enzyme and a palladium-catalysed aminocarbonylation reaction. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)00843-7

文献信息

• The Development of a Manufacturing Route for the GPIIb/IIIa Receptor Antagonist SB-214857-A. Part 2:  Conversion of the Key Intermediate SB-235349 to SB-214857-A
  作者：Richard J. Atkins、Adam Banks、Richard K. Bellingham、Gary F. Breen、John S. Carey、Stephen K. Etridge、Jerome F. Hayes、Nigel Hussain、David O. Morgan、Paul Oxley、Stephen C. Passey、Timothy C. Walsgrove、Andrew S. Wells

  DOI：10.1021/op034023k

  日期：2003.9.1

  The process development to the manufacturing route to (2S)-7-([4,4'-bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid hydrochloride (SB214857-A, lotrafiban) is described. The starting point is the previously reported intermediate (2RS)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester. The first stage is a lipase-catalysed resolution of the racemic ester to (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid and subsequent iodination using a pyridine iodine monochloride complex to give (2S)-2,3,4,5-tetrahydro-7-iodo-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid. The unreacted (R)-enantiomer of the starting ester is recovered and recycled to the racemate by treatment with sodium methoxide. The next stage describes the palladium-catalysed aminocarbonylation of the aryl iodide with 4,4'-pyridylpiperidine to give (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-7-[[4-(4-pyridinyl)-1-piperidinyl]carbonyl]-1H-1,4-benzodiazepine-2-acetic acid dihydrate. The third stage is the hydrogenation of the pyridine subunit over palladium on charcoal to obtain the zwitterionic (2S)-7-([4,4'-bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid hexahydrate. The final stage is the formation of the hydrochloride salt to afford the drug substance.
• Tetrahedron Lett. 2001, 42, 4915-4917
  作者：

  DOI：——

  日期：——
• ENZYMATIC RESOLUTION OF BENZODIAZEPINE-ACETIC ACID ESTERS WITH A LIPASE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0964928A1

  公开（公告）日：1999-12-22
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.