Potassium Carbonate → (4-Bromo-2-chloro-phenyl)-(4-fluoro-6-oxazol-5-yl-1H-benzoimidazol-5-yl)-amine

HRID 1676480노트

반응식

HRID 1676480 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH:25]=[O:26])=[CH:11][C:12]3[N:16]([CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:15]=[N:14][C:13]=3[C:23]=2[F:24])=[C:4]([Cl:27])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].S([CH2:44][N+:45]#[C-:46])(C1C=CC(C)=CC=1)(=O)=O>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:25]3[O:26][CH:46]=[N:45][CH:44]=3)=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:23]=2[F:24])=[C:4]([Cl:27])[CH:3]=1.[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:25]3[O:26][CH:46]=[N:45][CH:44]=3)=[CH:11][C:12]3[N:16]([CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:15]=[N:14][C:13]=3[C:23]=2[F:24])=[C:4]([Cl:27])[CH:3]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanide2회HCID 211142046-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehyde

생성물 2

HCID 11452548(4-Bromo-2-chloro-phenyl)-(4-fluoro-6-oxazol-5-yl-1H-benzoimidazol-5-yl)-amine수율 18%HCID 21114189(4-bromo-2-chloro-phenyl)-[4-fluoro-1-(2-methanesulfonyl-ethyl)-6-oxazol-5-yl-1H-benzoimidazol-5-yl]-amine수율 4%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehyde 10z (0.025 g, 0.053 mmol) is suspended in MeOH (2 mL) and K2CO3 (0.015 g, 0.105 mmol) is added followed by tosylmethyl isocyanide (0.011 g, 0.058 mmol). The reaction mixture is heated to reflux under N2 for 16 hours. After cooling, additional tosylmethyl isocyanide (0.011 g, 0.058 mmol) is added and the reaction mixture heated to reflux under N2 for 16 hours. The reaction mixture is cooled to room temperature, concentrated under reduced pressure and dissolved in ethyl acetate. The organic solution is washed with water and brine. The combined aqueous washes are extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography eluted with 20:1 methylene chloride:MeOH provides 4 mg (18%) desired product 10x and 1 mg (4%) (4-bromo-2-chloro-phenyl)-[4-fluoro-1-(2-methanesulfonyl-ethyl)-6-oxazol-5-yl-1H-benzoimidazol-5-yl]-amine.

후처리

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux under N2 for 16 hours
  3. temperatureAfter cooling
  4. temperaturethe reaction mixture heated
  5. temperatureto reflux under N2 for 16 hours
  6. concentrationconcentrated under reduced pressure
  7. dissolutiondissolved in ethyl acetate
  8. washThe organic solution is washed with water and brine
  9. extractionThe combined aqueous washes are extracted with ethyl acetate
  10. dry with materialThe combined organic extracts are dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customPurification by flash column chromatography
  13. washeluted with 20:1 methylene chloride

출처 및 근거

ORD 기록
ord-27ad2323accc44a69db03d9654f08211
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003805B2

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