*,R^*)>-<1-methyl-2-oxo-2-(3-pyrrolidinylamino)ethyl>carbamic acid 1,1-dimethylethyl ester | 122536-66-7

• 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: *,R^*)>-<1-methyl-2-oxo-2-(3-pyrrolidinylamino)ethyl>carbamic acid 1,1-dimethylethyl ester
• 英文别名: (S-(R^*,R^*))-[1-methyl-2-oxo-2-(3-pyrrolidinylamino)ethyl]carbamic acid 1,1-dimethylethyl ester；3-(S)-[2-(S)-(tert-butoxycarbonylamino)propionylamino]pyrrolidine；tert-butyl N-[(2S)-1-oxo-1-[[(3S)-pyrrolidin-3-yl]amino]propan-2-yl]carbamate
• CAS: 122536-66-7
• 化学式: C₁₂H₂₃N₃O₃
• 分子量: 257.333
• InChiKey: LUQCQTCJUWASKJ-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  *,R^*)>-<1-methyl-2-oxo-2-(3-pyrrolidinylamino)ethyl>carbamic acid 1,1-dimethylethyl ester 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 7.0h， 生成 5-Amino-7-[(S)-3-((S)-2-amino-propionylamino)-pyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid; hydrochloride
  参考文献：
  名称：

  Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity

  摘要：

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

  DOI：

  10.1021/jm00088a011
• 作为产物：
  描述：

  *,R^*)>-3-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-1-oxopropyl>amino>-1-pyrrolidinecarboxylic acid phenylmethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 24.5~25.5 ℃ 、355.77 kPa 条件下， 反应 3.0h， 以97%的产率得到*,R^*)>-<1-methyl-2-oxo-2-(3-pyrrolidinylamino)ethyl>carbamic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity

  摘要：

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

  DOI：

  10.1021/jm00088a011

文献信息

• Process for the manufacture of (S)-3-amino-1-substituted-pyrrolidines
  申请人：Warner-Lambert Company

  公开号：US05177217A1

  公开（公告）日：1993-01-05

  A novel process for preparing a stereospecific (S)-3-amino-1-substituted pyrrolidine used as a key intermediate in preparing quinolone and naphthyridone antibacterial agents where the 7-position is occupied with a sterospecific 3-amino-pyrrolidine side chain is described starting from inexpensive L-aspartic acid. L-aspartic acid is converted to the desired (S)-3-aminopyrrolidine via a novel, high yield transformation of a substituted aziridine.

  一种新的制备立体特异性(S)-3-氨基-1-取代吡咯烷的方法被描述，该化合物是制备喹诺酮和萘啶酮抗菌剂中7位被立体特异性3-氨基吡咯烷侧链占据的关键中间体。该方法从廉价的L-天冬氨酸开始，经过一种新颖的高产率取代环氮化合物转化，将L-天冬氨酸转化为所需的(S)-3-氨基吡咯烷。
• 1-Benzyl-3-(S)-[2-(S)-(tert-butoxy-carbonylamino) propionylamino] -pyrrolidine and its use as an intermediate
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0911322A2

  公开（公告）日：1999-04-28

  1-Benzyl-3(S)-[2-(S)-(tert.-butoxy-carbonylamino) propionylamino]-pyrrolidine and its use as an intermediate.

  1-Benzyl-3(S)-[2-(S)-(tert.-butoxy-carbonylamino) propionylamino]-pyrrolidine 及其作为中间体的用途。
• PROCESS FOR THE MANUFACTURE OF (S)-3-AMINO-1-SUBSTITUTED-PYRROLIDINES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0638068A1

  公开（公告）日：1995-02-15
• US5177217A
  申请人：——

  公开号：US5177217A

  公开（公告）日：1993-01-05
• US5250704A
  申请人：——

  公开号：US5250704A

  公开（公告）日：1993-10-05