N-Hydroxyacetamidine → N-(1-{[2-Chloro-5-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

HRID 1946385ノート

反応式

HRID 1946385 の反応式
[C:1](=[N:4][OH:5])([NH2:3])[CH3:2].[O-]CC.[Na+].[Cl:10][C:11]1[CH:20]=[CH:19][C:14]([C:15](OC)=O)=[CH:13][C:12]=1[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28]([C:30]2[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=2[F:37])=[O:29])=[N:23]1>C(O)C>[Cl:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]2[O:5][N:4]=[C:1]([CH3:2])[N:3]=2)=[CH:13][C:12]=1[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:29])[C:30]2[C:31]([F:37])=[CH:32][CH:33]=[CH:34][C:35]=2[F:36])=[N:23]1

参加物

5

反応物 3

HCID 30926N-HydroxyacetamidineHCID 2723922Sodium ethoxideHCID 59547941Methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate

生成物 1

HCID 59547977N-(1-{[2-Chloro-5-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒2 回

反応条件

温度
100 °C

実験手順

To a solution of acetamide oxime (89 mg, 1.20 mmol, GFS chemicals) in ethanol (2 ml) was added 4A activated molecular sieves (418 mg) (pre-dried in the oven overnight) and then 21% sodium ethoxide in ethanol (0.2 ml, 0.536 mmol, Alfa Aesar). To the reaction mixture was added methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate (for a preparation see Intermediate 23)(105 mg, 0.259 mmol). The reaction was heated to reflux (100° C.) and stirred for 3 h under nitrogen. The reaction mixture was evaporated in vacuo and the residue dissolved in methanol (0.5 ml) and filtered through a hydrophobic frit. The residue was dissolved with DMSO (0.5 ml) and the sample was purified by MDAP on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier (Method B). The solvent was evaporated in vacuo to give the title compound as a white gum (6.1 mg);

後処理

  1. temperatureThe reaction was heated
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue dissolved in methanol (0.5 ml)
  4. filtrationfiltered through a hydrophobic frit
  5. dissolutionThe residue was dissolved with DMSO (0.5 ml)
  6. customthe sample was purified by MDAP on Sunfire C18 column
  7. customThe solvent was evaporated in vacuo

出典と根拠

ORDレコード
ord-d0f332b905cd402c8c7614d7c25838a7
出典データセット
uspto-grants-2013_03
特許番号
US08399436B2

反応ノート

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