ethyl 4-{(2S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyrate | 1198149-97-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-{(2S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyrate
• 英文别名: 4-{(S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyric acid ethyl ester；1-Pyrrolidinebutanoic acid, 2-[[4-(4-chlorophenoxy)phenoxy]methyl]-, ethyl ester, (2S)-；ethyl 4-[(2S)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoate
• CAS: 1198149-97-1
• 化学式: C₂₃H₂₈ClNO₄
• 分子量: 417.933
• InChiKey: DJLYVTRWIBKMLR-IBGZPJMESA-N

物化性质

• 沸点：
  525.1±40.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-{(2S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyrate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以81.3%的产率得到(S)-4-(2-((4-(4-氯苯氧基)苯氧基)甲基)吡咯烷-1-基)丁酸
  参考文献：
  名称：

  Development of a Scalable Synthetic Process for DG-051B, A First-in-Class Inhibitior of LTA4H

  摘要：

  DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase H clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent four-step manufacturing sequence that has been used to manufacture at 100-kg scale. The entire process can be telescoped due to high conversion reactions, low impurity levels, efficient separations, and a very effective final purification. Two key aspects of the process are: (a) bypassing the isolation of a reactive electrophile by using its aqueous-washed reaction mixture directly into a coupling reaction with a phenoxide nucleophile and (b) modulating the properties of the final product solutions for optimal extraction, purification, and crystallization.

  DOI：

  10.1021/op900231j
• 作为产物：
  描述：

  N-Boc-L-脯氨醇 在 盐酸 、 4-二甲氨基吡啶 、 potassium tert-butylate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 90.0h， 生成 ethyl 4-{(2S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyrate
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING 4- { (S) -2- (4-(4-CHLOROPHENOXY) PHENOXYMETHYL) PYRROLIDIN-1-YL) } BUTYRIC ACID AND SALTS THEREOF
  [FR] PROCÉDÉ DE PRÉPARATION DE L'ACIDE 4-{(S)-2-(4-(4-CHLOROPHÉNOXY)PHÉNOXYMÉTHYL)PYRROLIDIN-1-YL}BUTYRIQUE ET DE SES SELS

  摘要：

  本发明涉及一种制备4-{(S)-2-[4-(4-氯苯氧基)苯氧甲基]吡咯烷-1-基}丁酸及其盐的方法。

  公开号：

  WO2011011598A1

文献信息

• Development of a Scalable Synthetic Process for DG-051B, A First-in-Class Inhibitior of LTA4H
  作者：Livia A. Enache、Isaac Kennedy、David W. Sullins、Wei Chen、Dragan Ristic、Glenn L. Stahl、Sergey Dzekhtser、Robert A. Erickson、Changren Yan、Frank W. Muellner、Michael D. Krohn、Jennifer Winger、Vincent Sandanayaka、Jasbir Singh、David E. Zembower、Alex S. Kiselyov

  DOI：10.1021/op900231j

  日期：2009.11.20

  DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase H clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent four-step manufacturing sequence that has been used to manufacture at 100-kg scale. The entire process can be telescoped due to high conversion reactions, low impurity levels, efficient separations, and a very effective final purification. Two key aspects of the process are: (a) bypassing the isolation of a reactive electrophile by using its aqueous-washed reaction mixture directly into a coupling reaction with a phenoxide nucleophile and (b) modulating the properties of the final product solutions for optimal extraction, purification, and crystallization.
• [EN] PROCESS FOR PREPARING 4- { (S) -2- (4-(4-CHLOROPHENOXY) PHENOXYMETHYL) PYRROLIDIN-1-YL) } BUTYRIC ACID AND SALTS THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE L'ACIDE 4-{(S)-2-(4-(4-CHLOROPHÉNOXY)PHÉNOXYMÉTHYL)PYRROLIDIN-1-YL}BUTYRIQUE ET DE SES SELS
  申请人：DECODE GENETICS EHF

  公开号：WO2011011598A1

  公开（公告）日：2011-01-27

  The present invention relates to a process for preparing 4-(S)-2-[4-(4-chlorophenoxy)phenoxymethyl]pyrrolidin-1-yl}butyric acid and its salts.

  本发明涉及一种制备4-(S)-2-[4-(4-氯苯氧基)苯氧甲基]吡咯烷-1-基}丁酸及其盐的方法。