ethyl (4-methoxyphenylamino)propyl ketone | 208646-48-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl (4-methoxyphenylamino)propyl ketone
• 英文别名: 6-(4-Methoxyanilino)hexan-3-one
• CAS: 208646-48-4
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: JLYDHQZPBDVZJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (4-methoxyphenylamino)propyl ketone 在 ammonium cerium (IV) nitrate 、 tetraphosphorus decasulfide 、 水 、 sodium ethanolate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 生成 7H-吡唑并[3,4-c]吡啶-7-硫酮,1-环戊基-3-乙基-1,4,5,6-四氢-
  参考文献：
  名称：

  Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine PDE-IV Inhibitor

  摘要：

  An efficient synthesis of the PDE IV inhibitor, 9H.-cyclopentyl.. 7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4-c]-1,2,4-triazolo-,5,6-dihydro-[4,3-a]pyridine I is described. Starting from commercially available gamma -caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with dimethyl sulfate and cesium carbonate in dimethylformamide, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4,c]pyridin-7- one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis.

  DOI：

  10.1021/op010222x
• 作为产物：
  描述：

  4-碘苯甲醚 在 铜 作用下， 以 乙醚 为溶剂， 生成 ethyl (4-methoxyphenylamino)propyl ketone
  参考文献：
  名称：

  Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine PDE-IV Inhibitor

  摘要：

  An efficient synthesis of the PDE IV inhibitor, 9H.-cyclopentyl.. 7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4-c]-1,2,4-triazolo-,5,6-dihydro-[4,3-a]pyridine I is described. Starting from commercially available gamma -caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with dimethyl sulfate and cesium carbonate in dimethylformamide, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4,c]pyridin-7- one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis.

  DOI：

  10.1021/op010222x

文献信息

• 7-Oxo-4,5,6,7-tetrahydro-1<i>H</i>-pyrazolo[3,4-<i>c</i>]pyridines as Novel Inhibitors of Human Eosinophil Phosphodiesterase
  作者：Allen J. Duplantier、Catharine J. Andresen、John B. Cheng、Victoria L. Cohan、Christian Decker、Frank M. DiCapua、Kenneth G. Kraus、Kerry L. Johnson、Claudia R. Turner、John P. UmLand、John W. Watson、Ronald T. Wester、Alison S. Williams、John A. Williams

  DOI：10.1021/jm9800090

  日期：1998.6.1

  High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 mu M. One such compound, CP-220,629 (22) (IC50 = 0.44 mu M), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1 beta (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).
• Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-<i>c</i>]-1,2,4-triazolo[4,3-<i>a</i>]pyridine PDE-IV Inhibitor
  作者：Frank J. Urban、Bruce G. Anderson、Susan L. Orrill、Peter J. Daniels

  DOI：10.1021/op010222x

  日期：2001.11.1

  An efficient synthesis of the PDE IV inhibitor, 9H.-cyclopentyl.. 7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4-c]-1,2,4-triazolo-,5,6-dihydro-[4,3-a]pyridine I is described. Starting from commercially available gamma -caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with dimethyl sulfate and cesium carbonate in dimethylformamide, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4,c]pyridin-7- one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis.