tert.-butyl (4S)-1-methyl-3-(2-bromo-n-butyryl)-2-oxo-imidazolidine-4-carboxylate | 195828-76-3

• 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
• 英文名称: tert.-butyl (4S)-1-methyl-3-(2-bromo-n-butyryl)-2-oxo-imidazolidine-4-carboxylate
• 英文别名: tert-butyl (4S)-3-(2-bromobutanoyl)-1-methyl-2-oxoimidazolidine-4-carboxylate
• CAS: 195828-76-3
• 化学式: C₁₃H₂₁BrN₂O₄
• 分子量: 349.225
• InChiKey: FLMKWEHCCBXOJD-GKAPJAKFSA-N

物化性质

• 沸点：
  378.9±52.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert.-butyl (4S)-1-methyl-3-(2-bromo-n-butyryl)-2-oxo-imidazolidine-4-carboxylate 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 29.0h， 生成 (S)-3-((R)-2-Carboxymethyl-butyryl)-1-methyl-2-oxo-imidazolidine-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Dynamic Kinetic Resolution Utilizing 2-Oxoimidazolidine-4-carboxylate as a Chiral Auxiliary:  Stereoselective Alkylation of α-Bromo Amides with Malonic Ester Enolates

  摘要：

  Stereoselective carbon-carbon bond formation by dynamic kinetic resolution using tert-butyl (4S)-1-methyl-2-oxoimidazolidine-4-carboxylate (1) as a chiral auxiliary was developed. Reaction of a diastereomeric mixture of tert-butyl (4S)-3-[(2RS)-2-bromoacyl]-1-methyl-2-oxoimidazolidine-4-carboxylates (2) with a malonic ester enolate in HMPA predominantly afforded tert-butyl (4S)-3-[(2R)-2-alkyl-3,3-bis(alkoxycarbonyl)propionyl]-1-methyl-2-oximidazolidine-4-carboxylate [(S,R)-8] in good yields. The stereoselectivity of this reaction was in accordance with our working hypothesis based on the conformational analysis of 2 and elucidated the unique characteristics of 1 as a novel chiral auxiliary for dynamic kinetic resolution. The alkylated products (S,R)-8ej,k were easily converted to chiral cx-alkyl succinic acid derivatives and chiral beta-amino acid derivatives, both of which have been known as key building blocks for the syntheses of a variety of biologically active compounds.

  DOI：

  10.1021/jo970484q
• 作为产物：
  描述：

  (4S)-3-苯甲氧羰基-1-甲基-2-氧代咪唑啉-4-羧酸叔丁酯 在 钯 potassium tert-butylate 、 氢气 作用下， 以 甲醇 为溶剂， -50.0~25.0 ℃ 、101.33 kPa 条件下， 反应 4.33h， 生成 tert.-butyl (4S)-1-methyl-3-(2-bromo-n-butyryl)-2-oxo-imidazolidine-4-carboxylate
  参考文献：
  名称：

  血管紧张素转化酶抑制剂的研究。4.3-酰基-1-烷基-2-氧代咪唑烷-4-羧酸衍生物的合成和血管紧张素转化酶抑制活性。

  摘要：

  通过两种方法制备（4S）-1-烷基-3-[[[N-（羧烷基）氨基]酰基] -2-氧代咪唑烷-4-羧酸衍生物（3）。评估了它们对血管紧张素转化酶（ACE）的抑制活性和降压作用，并讨论了它们之间的构效关系。具有S，S，S构型的二元羧酸3a-n显示出有效的体外ACE抑制活性，IC50值为1.1 X 10（-8）-1.5 X 10（-9）M.在该系列中最有效的化合物是单酯3p，ID50值为0.24 mg / kg，在正常血压大鼠中抑制血管紧张素I诱导的升压反应，在剂量为1-10 mg / kg时自发性高血压大鼠（SHRs）的收缩压呈剂量依赖性降低。公斤，磅

  DOI：

  10.1021/jm00122a003

文献信息

• Antihypertensive 2-oxo-imidazolidine derivatives
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04508727A1

  公开（公告）日：1985-04-02

  Novel 2-oxo-imidazolidine derivative of the formula: ##STR1## wherein R.sup.1 is lower alkyl or phenyl-lower alkyl, R.sup.2 is lower alkyl, R.sup.3 is alkyl of one to 12 carbon atoms or phenyl-lower alkyl and R.sup.4 is hydrogen or lower alkyl, and a pharmaceutically acceptable salts thereof are disclsoed. Said compounds (I) and salts thereof are useful as hypotensive agents.

  新型2-氧代咪唑烷酮衍生物的化学式为：##STR1## 其中R.sup.1是较低的烷基或苯基-较低的烷基，R.sup.2是较低的烷基，R.sup.3是碳原子数为1至12的烷基或苯基-较低的烷基，R.sup.4是氢或较低的烷基，以及其药学上可接受的盐被披露。所述化合物(I)及其盐对降压剂具有用途。
• Dynamic kinetic resolution of racemic α-halo acids via a chiral imidazolidinone auxiliary
  作者：Jeff A. O'Meara、Manfred Jung、Tony Durst

  DOI：10.1016/0040-4039(95)00339-e

  日期：1995.4

  A dynamic kinetic resolution is utilized to realize highly diastereoselective nucleophilic displacement of bromine in tert-butyl (4S)-1-methyl-3-(2-bromoacyl)-2-oxoimidazolidine-4-carboxylates (6a-f) by benzylamine enroute to tert-butyl (4S)-1-methyl-3-(2-benzyaminoacyl)-2-oxoimidazolidine-4-carboxylates (7a-e).

  利用动态动力学分辨率通过苄胺到（4S）-1-甲基-3-（2-溴酰基）-2-氧代咪唑烷-4-羧酸酯（6a-f）中实现对溴的高度非对映选择性亲核取代（4S）-1-甲基-3-（2-苯甲氨基酰基）-2-氧代咪唑烷-4-羧酸叔丁酯（7a-e）。
• Enantioselective Synthesis of β-Dibenzylamino Alcohols via a Dynamic Kinetic Resolution of α-Halo Acids
  作者：Jeff A. O'Meara、Nizar Gardee、Manfred Jung、Robert N. Ben、Tony Durst

  DOI：10.1021/jo9712714

  日期：1998.5.1
• Stereospecific Amination by Dynamic Kinetic Resolution Utilizing 2-Oxoimidazolidine-4-carboxylate as a Novel Chiral Auxiliary
  作者：Hitoshi Kubota、Akira Kubo、Masami Takahashi、Ryo Shimizu、Tadamasa Da-te、Kimio Okamura、Ken-ichi Nunami

  DOI：10.1021/jo00126a029

  日期：1995.10

  A novel type of stereospecific amination by dynamic kinetic resolution using (4S)-2-oxoimidazolidine-4-carboxylate (1) as a chiral auxiliary was developed. A reaction of a diastereomeric mixture of (4S)-3-[(2RS)-2-bromoacyl]-2-oxoimidazolidine-4-carboxylates 4 with an amine in the presence of a base in HMPA predominantly afforded (4S)-3-[(2R)-2-(alkylamino)acyl]-2-oxoimidazolidine-4-carboxylates (S,R)-7 in good yields. The reaction proceeded by stereospecific S(N)2 type amination incorporated with rapid interconversion between the substrates (S,S)-4 and (S,R)-4. Mechanistic study suggested that the unique stereoselectivity was induced through the interaction between an amine and the ester group of (S,S)-4 in the transition state. The chiral auxiliary was easily removed with alkoxide anion to afford the alpha-amino acid synthon in good yields.
• Dynamic kinetic resolution utilizing 2-oxoimidazolidine-4-carboxylate as a chiral auxiliary: Stereoselective synthesis of α-amino acids by Gabriel reaction
  作者：Akira Kubo、Hitoshi Kubota、Masami Takahashi、Ken-ichi Nunami

  DOI：10.1016/0040-4039(96)00977-x

  日期：1996.7

  A Highly stereoselective Gabriel reaction via dynamic kinetic resolution utilizing 2-oxoimidazolidine-4-carboxylate as a chiral auxiliary was exploited. The reaction of tert-butyl (4S)-1-methyl-3-(2-bromopropionyl)-2-oxoimidazolidine-4- carboxylate (2a) with potassium phthalimide at room temperature predominantly afforded tert-butyl (4S)-1-methyl-3-((2S)-2-(phthaloylamino)propionyl)-2- oxoimidazolidine-4-carboxylate ((S,S)-5a) in a good yield which was derived to L-alanine derivative (7) by removal of the chiral auxiliary. Copyright (C) 1996 Elsevier Science Ltd.