Dimethyl Sulfoxide → 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-methanesulfonyl-pyridin-3-yl)-butyl]-amide

HRID 2067976ノート

反応式

HRID 2067976 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=[N:6][CH:7]=1.[CH3:28][S:29]([O-:31])=[O:30].[Na+].CS(C)=O.CNCCNC>CCOC(C)=O.[O-]S(C(F)(F)F)(=O)=O.[Cu+2].[O-]S(C(F)(F)F)(=O)=O>[CH3:28][S:29]([C:2]1[CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=[N:6][CH:7]=1)(=[O:31])=[O:30]

参加物

7

反応物 4

HCID 679Dimethyl SulfoxideHCID 8070N,N'-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 444805971-(4-Chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amide

生成物 1

HCID 444806001-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-methanesulfonyl-pyridin-3-yl)-butyl]-amide収率 30.5%

試薬・触媒・溶媒 2

HCID 2734996copper(II) trifluoromethanesulfonate触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

1-(4-Chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amide (100 mg, 0.22 mmol), copper(II) triflate (81 mg, 0.22 mmol), sodium methylsulfinate (80 mg, 0.67 mmol) are added to a reaction vial with a septum top which is then evacuated and filled with nitrogen for 3 cycles. DMSO (1 mL) and N,N′-dimethylethylenediamine (71 μL, 0.67 mmol) are added and the reaction is heated at 100° C. for 30 hours. The resultant mixture is cooled to room temperature, diluted with EtOAc (50 mL), and washed with saturated aqueous ammonium chloride (2×25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL). The combined organic layers are dried over magnesium sulfate, filtered and concentrated in vacuo. The crude material is purified by preparative reverse phase HPLC (eluted with 10 to 95% CH3CN/H2O and 0.1% TFA as additive) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-methanesulfonyl-pyridin-3-yl)-butyl]-amide as a colorless foam (30 mg, 30%).

後処理

  1. customis then evacuated
  2. additionfilled with nitrogen for 3 cycles
  3. washwashed with saturated aqueous ammonium chloride (2×25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL)
  4. dry with materialThe combined organic layers are dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material is purified by preparative reverse phase HPLC (eluted with 10 to 95% CH3CN/H2O and 0.1% TFA as additive)

出典と根拠

ORDレコード
ord-4f44820043514a64861dea8f65e46e79
出典データセット
uspto-grants-2012_10
特許番号
US08293917B2

反応ノート

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