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

HRID 504232ノート

反応式

HRID 504232 の反応式
[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

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanide2 回HCID 211142046-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carbaldehyde

生成物 2

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d9a7e66f7e824957abf9368de32869a5
出典データセット
uspto-grants-2010_08
特許番号
US07777050B2

反応ノート

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