Iodoethane → 4-ethyl-6-{[3-fluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

HRID 519934

反応式

HRID 519934 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:22]2[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:21])[NH:11][C:12]2[N:13]([N:18]=[CH:19][N:20]=2)[C:14]=1[CH2:15][CH2:16][CH3:17].I[CH2:31][CH3:32].[C:33](=[O:36])([O-])[O-:34].[K+].[K+].[Cl-].O[NH3+:41].C(=O)([O-])O.[Na+]>C(OCC)(=O)C.CS(C)=O.CN(C)C=O>[CH2:31]([N:11]1[C:10](=[O:21])[C:9]([CH2:8][C:7]2[CH:6]=[CH:5][C:4]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3[NH:41][C:33](=[O:36])[O:34][N:29]=3)=[CH:3][C:2]=2[F:1])=[C:14]([CH2:15][CH2:16][CH3:17])[N:13]2[N:18]=[CH:19][N:20]=[C:12]12)[CH3:32]

参加物

9

反応物 5

HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 1363371393'-Fluoro-4'-[(5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile

生成物 1

HCID 1360637574-ethyl-6-{[3-fluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one収率 8%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

A mixture of 3′-fluoro-4′-[(5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (1 g), iodoethane (0.25 mL), potassium carbonate (0.71 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in dimethyl sulfoxide (5 mL), and the mixture was added to a mixture of hydroxylammonium chloride (0.4 g), sodium hydrogen carbonate (0.65 g) and dimethyl sulfoxide (5 mL), which had been stirred in advance at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, and diluted with ethyl acetate, and the mixture was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.063 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.1 g, 8%).

後処理

  1. washwashed with 5% aqueous potassium hydrogensulfate solution
  2. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customThe residue obtained by silica gel column chromatography
  5. stirringhad been stirred in advance at 40° C. for 30 min
  6. stirringThe reaction mixture was stirred at 90° C. for 16 hr
  7. washthe mixture was washed with water
  8. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
  11. additionN,N′-Carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.063 mL) were added
  12. stirringthe mixture was stirred at room temperature for 2 hr
  13. additionThe reaction mixture was diluted with ethyl acetate
  14. washwashed with saturated aqueous potassium hydrogensulfate solution
  15. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated under reduced pressure
  17. customthe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-221a98bcf2de4de492ed84ee6b61efab
出典データセット
uspto-grants-2015_08
特許番号
US09115136B2

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