Water → (S)-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1-(3-oxobutyl)-1H-imidazole-4-carboxamide

HRID 872844ノート

反応式

HRID 872844 の反応式
CN1C=CN=C1.[Cl:7][C:8]1[CH:9]=[C:10]([C:17]2[CH:21]=[CH:20][N:19]([CH2:22][C@@H:23]([NH:25][C:26]([C:28]3[N:29]=[C:30]([CH3:33])[NH:31][CH:32]=3)=[O:27])[CH3:24])[N:18]=2)[CH:11]=[C:12]([F:16])[C:13]=1[C:14]#[N:15].[CH:34]([C:36]([CH3:38])=[O:37])=[CH2:35].O>CS(C)=O>[Cl:7][C:8]1[CH:9]=[C:10]([C:17]2[CH:21]=[CH:20][N:19]([CH2:22][C@@H:23]([NH:25][C:26]([C:28]3[N:29]=[C:30]([CH3:33])[N:31]([CH2:35][CH2:34][C:36](=[O:37])[CH3:38])[CH:32]=3)=[O:27])[CH3:24])[N:18]=2)[CH:11]=[C:12]([F:16])[C:13]=1[C:14]#[N:15]

参加物

6

反応物 4

HCID 962WaterHCID 13901-Methylimidazole2 回HCID 6570Methyl vinyl ketone2 回HCID 178433049HCID 178433049、化合物

生成物 1

HCID 66576682(S)-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1-(3-oxobutyl)-1H-imidazole-4-carboxamide収率 42.3%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒2 回

反応条件

温度
70 °C

実験手順

1-Methylimidazole (1.030 μl, 0.013 mmol) and DMSO (3 ml) were added into a flask. (S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide (100 mg, 0.259 mmol) dissolved in 3 ml of DMSO was added. Lastly methyl vinyl ketone (0.065 ml, 0.776 mmol) was added and the resulting mixture was stirred in 70° C. for 2.5 h. The mixture was stirred at RT during the night and in the next morning the temperature was again raised to 70° C. for 3.5 h. During the last part of the reaction a total of 0.195 ml of methyl vinyl ketone and 16.48 μl of 1-methylimidazole were added and the mixture was stirred at 70° C. for three days. 10 ml of water was poured into the mixture and the resulting white solution was extracted with ethyl acetate. Combined ethyl acetate phases were dried, filtered and evaporated. The product was purified by flash-chromatography and recrystallization from ACN/water, respectively. Yield 42.3%. 1H-NMR (400 MHz; DMSO-d6): δ 1.05 (d, 3H), 2.09 (s, 3H), 2.35 (s, 3H), 2.97 (t, 2H), 4.04 (t, 2H), 4.23-4.45 (m, 3H), 7.01 (d, 1H), 7.48 (s, 1H), 7.85 (d, 1H), 7.93 (dd, 1H), 8.00 (s, 1H), 8.05 (d, 1H).

後処理

  1. additionwas added
  2. stirringThe mixture was stirred at RT during the night and in the next morning the temperature
  3. temperaturewas again raised to 70° C. for 3.5 h
  4. additionwere added
  5. stirringthe mixture was stirred at 70° C. for three days
  6. extractionthe resulting white solution was extracted with ethyl acetate
  7. dry with materialCombined ethyl acetate phases were dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe product was purified by flash-chromatography and recrystallization from ACN/water

出典と根拠

ORDレコード
ord-a0e8655fedaa4ff7af83c07358d9f8f1
出典データセット
uspto-grants-2015_03
特許番号
US08975254B2

反応ノート

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