N-(1-phenylbutylidene)-1-propanamine | 321864-77-1

• 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: N-(1-phenylbutylidene)-1-propanamine
• 英文别名: 1-phenyl-N-propylbutan-1-imine
• CAS: 321864-77-1
• 化学式: C₁₃H₁₉N
• 分子量: 189.301
• InChiKey: FYGRPVGJGXLJLK-UHFFFAOYSA-N

物化性质

• 沸点：
  260.0±13.0 °C(Predicted)
• 密度：
  0.87±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(1-phenylbutylidene)-1-propanamine 在 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 (R,S)-1-propylamino-1-phenylbutane
  参考文献：
  名称：

  Rational Design, Synthesis, and Structure−Activity Relationships of Aryltriazoles as Novel Corticotropin-Releasing Factor-1 Receptor Antagonists

  摘要：

  Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF1) (e.g., 1, K-i = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine followed by alkylation. While members of this series showed potent binding affinity against CRF1 receptor, there were important differences between the different regio- (7 and 12) and stereoisomeric aryltriazoles where the R-1 or R-2 side chain in 7 has an asymmetric center. In terms of overall potency, aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N-propylamino side chain were the most potent, followed by analogues such as 7a, with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as 7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N-propyl group was crucial for high potency, we hypothesized that the terminal methyl mimicked the 5-methyl of pyrazolo[1,5-alpha]pyrimidines 3 and 4. Correlation of the low-energy conformers of compounds of type 3 and 7 generated by computational analyses was very good. The size and shape of the N-alkyl group dramatically changed the potency of the triazoles, which is in contrast to the SAR seen for bicyclic CRF1 antagonists. In general, the S-enantiomer was much more potent than the corresponding R-isomer. Furthermore, to a limited extent in the aryltriazole series the substituent on the 5-phenyl ring changed the potency up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2-methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding affinity (K-i = 2.7 nM) to CRF1 receptors with an IC50 of 49 nM in a cAMP inhibition assay.

  DOI：

  10.1021/jm049339c
• 作为产物：
  描述：

  正丙胺 、 苯丁酮 在 四氯化钛 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以92%的产率得到N-(1-phenylbutylidene)-1-propanamine
  参考文献：
  名称：

  方便的一锅合成亚胺，维斯迈尔型试剂和肼的吡唑

  摘要：

  描述了一种简单的一锅法，用于从容易获得的起始原料进行区域选择性合成吡唑。Vilsmeier型试剂1与亚胺10（通过相应的互变异构仲烯胺）在四氢呋喃中反应，得到烯氨基亚胺盐酸盐11。非对称亚胺通常在空间受阻较小的α位置优先与1反应。通过加入肼，将烯氨基亚胺盐酸盐11以中等至高产率原位转化为相应的吡唑12。

  DOI：

  10.1002/jhet.5570370548

文献信息

• Rational Design, Synthesis, and Structure−Activity Relationships of Aryltriazoles as Novel Corticotropin-Releasing Factor-1 Receptor Antagonists
  作者：Richard F. Lowe、Jodene Nelson、Trunghau N. Dang、Paul D. Crowe、Anil Pahuja、James R. McCarthy、Dimitri E. Grigoriadis、Paul Conlon、John Saunders、Chen、Thomas Szabo、Ta Kung Chen、Haig Bozigian

  DOI：10.1021/jm049339c

  日期：2005.3.1

  Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF1) (e.g., 1, K-i = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine followed by alkylation. While members of this series showed potent binding affinity against CRF1 receptor, there were important differences between the different regio- (7 and 12) and stereoisomeric aryltriazoles where the R-1 or R-2 side chain in 7 has an asymmetric center. In terms of overall potency, aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N-propylamino side chain were the most potent, followed by analogues such as 7a, with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as 7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N-propyl group was crucial for high potency, we hypothesized that the terminal methyl mimicked the 5-methyl of pyrazolo[1,5-alpha]pyrimidines 3 and 4. Correlation of the low-energy conformers of compounds of type 3 and 7 generated by computational analyses was very good. The size and shape of the N-alkyl group dramatically changed the potency of the triazoles, which is in contrast to the SAR seen for bicyclic CRF1 antagonists. In general, the S-enantiomer was much more potent than the corresponding R-isomer. Furthermore, to a limited extent in the aryltriazole series the substituent on the 5-phenyl ring changed the potency up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2-methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding affinity (K-i = 2.7 nM) to CRF1 receptors with an IC50 of 49 nM in a cAMP inhibition assay.
• Convenient one-pot syntheses of pyrazoles from imines, a vilsmeier type reagent and hydrazine
  作者：Alan R. Katritzky、Anna Denisenko、Sergey N. Denisenko、Michael Arend

  DOI：10.1002/jhet.5570370548

  日期：2000.9

  one-pot procedure for the regioselective synthesis of pyrazoles from readily available starting materials is described. Vilsmeier type reagent 1 reacts with imines 10 (via the corresponding tautomeric secondary enamines) in tetrahydrofuran to give enaminoimine hydrochlorides 11. Nonsymmetrical imines generally react preferentially with 1 at the sterically less hindered α-position. The enaminoimine hydrochlorides

  描述了一种简单的一锅法，用于从容易获得的起始原料进行区域选择性合成吡唑。Vilsmeier型试剂1与亚胺10（通过相应的互变异构仲烯胺）在四氢呋喃中反应，得到烯氨基亚胺盐酸盐11。非对称亚胺通常在空间受阻较小的α位置优先与1反应。通过加入肼，将烯氨基亚胺盐酸盐11以中等至高产率原位转化为相应的吡唑12。