1-benzoyl-2-(cyanomethyl)proline methyl ester | 128243-98-1

• 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: 1-benzoyl-2-(cyanomethyl)proline methyl ester
• 英文别名: methyl 1-benzoyl-2-(nitrilomethyl)pyrrolidine-2-carboxylate；methyl 1-benzoyl-2-cyanomethylpyrrolidine-2-carboxylate；methyl 1-benzoyl-2-(cyanomethyl)pyrrolidine-2-carboxylate
• CAS: 128243-98-1
• 化学式: C₁₅H₁₆N₂O₃
• 分子量: 272.304
• InChiKey: WYALMMDNESIBLT-UHFFFAOYSA-N

物化性质

• 沸点：
  453.7±30.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  70.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzoyl-2-(cyanomethyl)proline methyl ester 在 镍 lithium aluminium tetrahydride 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 25.0~50.0 ℃ 、344.73 kPa 条件下， 反应 96.0h， 生成 1-苄基-1,7-二氮杂螺[4.4]壬烷
  参考文献：
  名称：

  Quinolone antibacterial agents substituted at the 7-position with spiroamines. Synthesis and structure-activity relationships

  摘要：

  A series of fluoroquinolone antibacterials having the 7-position (10-position of pyridobenzoxazines) substituted with 2,7-diazaspiro[4.4]nonane (4b), 1,7-diazaspiro[4.4]nonane (5a), or 2,8-diazaspiro[5.5]undecane (6b) was prepared, and their biological activities were compared with piperazine and pyrrolidine substituted analogues. Most exhibited potent Gram-positive and Gram-negative activity, especially when side chain 4b was N-alkylated.

  DOI：

  10.1021/jm00170a035
• 作为产物：
  描述：

  N-苯甲酰基-l-脯氨酸 在 氯化亚砜 、 四甲基乙二胺 、 lithium diisopropyl amide 作用下， 反应 2.17h， 生成 1-benzoyl-2-(cyanomethyl)proline methyl ester
  参考文献：
  名称：

  Quinolone antibacterial agents substituted at the 7-position with spiroamines. Synthesis and structure-activity relationships

  摘要：

  A series of fluoroquinolone antibacterials having the 7-position (10-position of pyridobenzoxazines) substituted with 2,7-diazaspiro[4.4]nonane (4b), 1,7-diazaspiro[4.4]nonane (5a), or 2,8-diazaspiro[5.5]undecane (6b) was prepared, and their biological activities were compared with piperazine and pyrrolidine substituted analogues. Most exhibited potent Gram-positive and Gram-negative activity, especially when side chain 4b was N-alkylated.

  DOI：

  10.1021/jm00170a035

文献信息

• [EN] PREPARATION AND ENANTIOMERIC SEPARATION OF 7-(3-PYRIDINYL)-1,7-DIAZASPIRO[4.4] NONANE AND NOVEL SALT FORMS OF THE RACEMATE AND ENANTIOMERS<br/>[FR] PRÉPARATION ET SÉPARATION ÉNANTIOMÉRIQUE DE NONANE DE 7-(3-PYRIDINYL)-1,7-DIAZASPIRO[4.4] ET NOUVELLES FORMES DE SEL DU RACÉMATE ET D'ÉNANTIOMÈRES
  申请人：TARGACEPT INC

  公开号：WO2009091561A1

  公开（公告）日：2009-07-23

  A novel scalable synthesis for the preparation of 7-(3- pyridinyI)- 1,7- diazaspiro[4.4)nonane has been developed, and7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane salts have been formed with succinic acid and oxalic acid. Additionally, 7-(3-pyridinyl)-1,7- diazaspiro[4.4]nonane has been separated into its stereoisomers via resolution with L and D di-p-toluoyltartaric acids, giving (R)- and (S)-7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane of high enantiomeric purity. Numerous solid salts of the resulting (R)- and (S)-7-(3-pyridinyl)-1,7- diazaspiro[4.4}nonane have been prepared. Methods for the preparation of the racemic and enantiomeric salts, pharmaceutical compositions comprising such salts, and uses thereof are disclosed. The salts can be administered to patients susceptible to or suffering from conditions and disorders, such as central nervous system disorders, to treat and/or prevent such disorders.

  已开发一种新型可扩展的合成方法，用于制备7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷，并用琥珀酸和草酸形成了7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷盐。此外，通过与L和D二对甲苯甲酰酒石酸进行分离，将7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷分离为其立体异构体，得到高对映纯度的(R)-和(S)-7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷。已制备了大量由(R)-和(S)-7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷产生的固体盐。公开了制备外消旋和对映体盐的方法，包括含有这些盐的药物组合物以及其用途。这些盐可用于治疗和/或预防中枢神经系统疾病等疾病和疾病，可向易感患者或患有这些疾病和紊乱的患者施用。
• PREPARATION AND ENANTIOMERIC SEPARATION OF 7-(3-PYRIDINYL)-1,7-DIAZASPIRO[4.4]NONANE AND NOVEL SALT FORMS OF THE RACEMATE AND ENANTIOMERS
  申请人：Beaver Jessica

  公开号：US20110118239A1

  公开（公告）日：2011-05-19

  A novel scalable synthesis for the preparation of 7-(3-pyridinyI)-1,7-diazaspiro[4.4)nonane has been developed, and 7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane salts have been formed with succinic acid and oxalic acid. Additionally, 7-(3-pyridinyl)-1,7-diaza-spiro[4.4]nonane has been separated into its stereoisomers via resolution with L and D di-p-toluoyltartaric acids, giving (R)- and (S)-7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane of high enantiomeric purity. Numerous solid salts of the resulting (R)- and (S)-7-(3-pyridinyl)-1,7-diazaspiro[4.4}nonane have been prepared. Methods for the preparation of the racemic and enantiomeric salts, pharmaceutical compositions comprising such salts, and uses thereof are disclosed. The salts can be administered to patients susceptible to or suffering from conditions and disorders, such as central nervous system disorders, to treat and/or prevent such disorders.

  已开发一种新的可扩展合成方法，用于制备7-(3-吡啶基)-1，7-二氮杂螺[4.4]壬烷，并且已经用琥珀酸和草酸形成了7-(3-吡啶基)-1，7-二氮杂螺[4.4]壬烷盐。此外，通过与L和D双对甲苯基酞酸进行分离，已将7-(3-吡啶基)-1，7-二氮杂螺[4.4]壬烷分离为其立体异构体，得到高对映纯度的(R)-和(S)-7-(3-吡啶基)-1，7-二氮杂螺[4.4]壬烷。已制备出许多由(R)-和(S)-7-(3-吡啶基)-1，7-二氮杂螺[4.4]壬烷形成的固态盐。公开了制备外消旋盐和对映体盐的方法，以及包含这些盐的制药组合物和其用途。这些盐可用于治疗和/或预防中枢神经系统疾病等病症和障碍的易感患者。
• [EN] SUBSTITUTED 2-HYDROGEN-PYRAZOLE DERIVATIVE SERVING AS ANTICANCER DRUG<br/>[FR] DÉRIVÉ DE 2-HYDROGÈNE-PYRAZOLE SUBSTITUÉ SERVANT DE MÉDICAMENT ANTICANCÉREUX<br/>[ZH] 作为抗癌药物的取代的2-氢-吡唑衍生物
  申请人：MEDSHINE DISCOVERY INC

  公开号：WO2016141881A1

  公开（公告）日：2016-09-15

  本发明公开了作为选择性的CDK4/6抑制剂取代的2-氢-吡唑衍生物。具体地讲，本发明涉及作为选择性的CDK4/6抑制剂的式(I)或其药学上可接受的盐。
• SUBSTITUTED 2-HYDROGEN-PYRAZOLE DERIVATIVE SERVING AS ANTICANCER DRUG
  申请人：Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

  公开号：EP3269715B1

  公开（公告）日：2020-05-13
• CULBERTSON, TOWNLEY P.;SANCHEZ, JOSEPH P.;GAMBINO, LAURA;SESNIE, JOSEPHIN+, J. MED. CHEM., 33,(1990) N, C. 2270-2275
  作者：CULBERTSON, TOWNLEY P.、SANCHEZ, JOSEPH P.、GAMBINO, LAURA、SESNIE, JOSEPHIN+

  DOI：——

  日期：——