2-(Tributylstannyl)furan → 2-Cyclopropyl-7-fluoro-6-(2-furyl)-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17331

反応式

HRID 17331 の反応式
Br[C:2]1[C:3]([F:17])=[C:4]2[O:8][C:7]([CH:9]3[CH2:11][CH2:10]3)=[N:6][C:5]2=[C:12]([C:15]#[N:16])[C:13]=1[CH3:14].C([Sn](CCCC)(CCCC)[C:23]1[O:24][CH:25]=[CH:26][CH:27]=1)CCC>C1C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(C1(C)C(O)=C(C(C)(C)C)C=CC1)(C)(C)C>[CH:9]1([C:7]2[O:8][C:4]3[C:5](=[C:12]([C:15]#[N:16])[C:13]([CH3:14])=[C:2]([C:23]4[O:24][CH:25]=[CH:26][CH:27]=4)[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1

参加物

6

反応物 2

HCID 43936882-(Tributylstannyl)furanHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

生成物 1

HCID 685862542-Cyclopropyl-7-fluoro-6-(2-furyl)-5-methyl-1,3-benzoxazole-4-carbonitrile収率 100%

試薬・触媒・溶媒 3

HCID 666371922,6-Di-t-butylcresol触媒HCID 178418476HCID 178418476、化合物触媒HCID 241Benzene溶媒

実験手順

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (100 mg, 0.34 mmol) was dissolved in benzene (3 ml), then 2-tributylstannylfuran (117 μl, 0.37 mmol) and 2,6-di-tert-butylcresol (1 mg) and bis(triphenylphosphine)palladium(II) dichloride (3 mg, 0.003 mmol) were added, followed by hearing under reflux for 20 hours under nitrogen atmosphere. The reaction liquid was cooled, the insoluble matter was separated by filtration through Celite, the solvent was concentrated under reduced pressure. The resulting residue was fractionated with ethyl acetate and water, followed by washing with saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure. The resulting residue was dissolved in methylene chloride, potassium fluoride (20 mg) and water (0.1 ml) were added, followed by vigorously stirring at room temperature for 30 hours. The insoluble matter was separated by filtration through Celite, followed by fractionation with methylene chloride and water and by washing with saturated brine. The obtained organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography, eluted with a mixed solvent of n-hexane/ethyl acetate (3:1, v/v) to obtain 2-cyclopropyl-7-fluoro-6-(2-furyl)-5-methyl-1,3-benzoxazole-4-carbonitrile (96 mg) as a white solid. This was dissolved in dimethyl sulfoxide (2 ml), triethylamine (119 μl, 0.85 mmol) and (3S)-3-(dimethylamino)pyrrolidine (56 μl, 0.44 mmol) were added, followed by stirring at 90° C. under nitrogen atmosphere for 22 hours. After cooling to room temperature, ethyl acetate was added, followed by fractionation with water. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated away, the resulting residue was subjected to preparative thin-layer silica gel column chromatography and eluted with a mixed solvent of chloroform/methanol (20:1, v/v) to obtain the entitled compound (37 mg, 29%) as a white solid.

後処理

  1. temperatureunder reflux for 20 hours under nitrogen atmosphere
  2. customThe reaction liquid
  3. temperaturewas cooled
  4. customthe insoluble matter was separated by filtration through Celite
  5. concentrationthe solvent was concentrated under reduced pressure
  6. washby washing with saturated brine
  7. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  8. customthe solvent was evaporated away under reduced pressure
  9. dissolutionThe resulting residue was dissolved in methylene chloride
  10. additionpotassium fluoride (20 mg) and water (0.1 ml) were added
  11. customThe insoluble matter was separated by filtration through Celite
  12. washby washing with saturated brine
  13. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  14. customthe solvent was evaporated away under reduced pressure
  15. washeluted with a mixed solvent of n-hexane/ethyl acetate (3:1

出典と根拠

ORDレコード
ord-3ddcb8ed03e14501afddba9d81c744c8
出典データセット
uspto-grants-2010_06
特許番号
US07737166B2

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