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 872844노트

반응식

HRID 872844 반응식
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]

참가 물질

6

반응물 4

HCID 962WaterHCID 13901-Methylimidazole2회HCID 6570Methyl vinyl ketone2회HCID 178433049HCID 178433049, 화합물

생성물 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-carboxamide수율 42.3%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매2회

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온도
70 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a0e8655fedaa4ff7af83c07358d9f8f1
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975254B2

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