(+)-methyl (2S)-2-(3-chloropropanoylamino)-3-hydroxypropanoate | 1145667-63-5

• 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: (+)-methyl (2S)-2-(3-chloropropanoylamino)-3-hydroxypropanoate
• 英文别名: methyl (2S)-2-(3-chloropropanoylamino)-3-hydroxypropanoate
• CAS: 1145667-63-5
• 化学式: C₇H₁₂ClNO₄
• 分子量: 209.63
• InChiKey: IKKJLDQGPCZFFJ-YFKPBYRVSA-N

物化性质

• 沸点：
  424.0±40.0 °C(predicted)
• 密度：
  1.287±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-methyl (2S)-2-(3-chloropropanoylamino)-3-hydroxypropanoate 、 苯甲醛二甲缩醛 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 methyl (2R,4S)-3-(3-chloropropanoyl)-2-phenyl-1,3-oxazolidine-4-carboxylate 、 methyl (2S,4S)-3-(3-chloropropanoyl)-2-phenyl-1,3-oxazolidine-4-carboxylate
  参考文献：
  名称：

  1,4-Diazepanes derived from (S)-serine – Homopiperazines with improved σ1 (sigma) receptor affinity and selectivity

  摘要：

  Starting from the proteinogenic amino acid (S)-serine chiral non-racemic 1,4-diazepanes 4 with a hydroxymethyl residue in position 2 are synthesized and pharmacologically evaluated. The key step in the synthesis is the formation of the bicyclic system 8 by consecutive nucleophilic substitution of the chloropropionamide 7 with primary amines and intramolecular aminolysis. Both reaction steps require catalysis with the Lewis acid Ti(O-iPr)(4). Homologation of the piperazine to the 1,4-diazepane ring results in a remarkable improvement of sigma(1) receptor affinity and sigma(1)/sigma(2) selectivity. The 1,4-dibenzyl derivative 4a interacts with a K-i value of 7.4 nM with sigma(1) receptors and shows a 53-fold selectivity for sigma(1) receptors over sigma(2) receptors. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.033
• 作为产物：
  描述：

  L-丝氨酸甲酯盐酸盐 、 3-氯丙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到(+)-methyl (2S)-2-(3-chloropropanoylamino)-3-hydroxypropanoate
  参考文献：
  名称：

  1,4-Diazepanes derived from (S)-serine – Homopiperazines with improved σ1 (sigma) receptor affinity and selectivity

  摘要：

  Starting from the proteinogenic amino acid (S)-serine chiral non-racemic 1,4-diazepanes 4 with a hydroxymethyl residue in position 2 are synthesized and pharmacologically evaluated. The key step in the synthesis is the formation of the bicyclic system 8 by consecutive nucleophilic substitution of the chloropropionamide 7 with primary amines and intramolecular aminolysis. Both reaction steps require catalysis with the Lewis acid Ti(O-iPr)(4). Homologation of the piperazine to the 1,4-diazepane ring results in a remarkable improvement of sigma(1) receptor affinity and sigma(1)/sigma(2) selectivity. The 1,4-dibenzyl derivative 4a interacts with a K-i value of 7.4 nM with sigma(1) receptors and shows a 53-fold selectivity for sigma(1) receptors over sigma(2) receptors. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.033

文献信息

• 1,4-Diazepanes derived from (S)-serine – Homopiperazines with improved σ1 (sigma) receptor affinity and selectivity
  作者：Stephan Bedürftig、Bernhard Wünsch

  DOI：10.1016/j.ejmech.2008.03.033

  日期：2009.2

  Starting from the proteinogenic amino acid (S)-serine chiral non-racemic 1,4-diazepanes 4 with a hydroxymethyl residue in position 2 are synthesized and pharmacologically evaluated. The key step in the synthesis is the formation of the bicyclic system 8 by consecutive nucleophilic substitution of the chloropropionamide 7 with primary amines and intramolecular aminolysis. Both reaction steps require catalysis with the Lewis acid Ti(O-iPr)(4). Homologation of the piperazine to the 1,4-diazepane ring results in a remarkable improvement of sigma(1) receptor affinity and sigma(1)/sigma(2) selectivity. The 1,4-dibenzyl derivative 4a interacts with a K-i value of 7.4 nM with sigma(1) receptors and shows a 53-fold selectivity for sigma(1) receptors over sigma(2) receptors. (C) 2008 Elsevier Masson SAS. All rights reserved.