Hydroxylamine HCl → 6-butyl-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2-phenylpropyl)pyrimidin-4(3H)-one

HRID 1718431노트

반응식

HRID 1718431 반응식
[CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].Br[CH2:31][CH:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH3:33].[Cl-].O[NH3+:42].[C:43](=[O:46])([O-])[OH:44].[Na+]>C(OCC)(=O)C.CS(C)=O.CN(C)C=O>[CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[N:8]([CH2:31][CH:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH3:33])[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]2[NH:42][C:43](=[O:46])[O:44][N:25]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]

참가 물질

9

반응물 5

HCID 21645Hydroxylamine HClHCID 24758Sodium hydrideHCID 978131-Bromo-2-phenylpropaneHCID 516892Sodium BicarbonateHCID 1354012224'-[(4-Butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile

생성물 1

HCID 1360268706-butyl-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2-phenylpropyl)pyrimidin-4(3H)-one수율 9%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매2회HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회

실험 절차

A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1 g), sodium hydride (0.17 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 10 min, (2-bromo-1-methylethyl)benzene (1.1 g) was added, and the mixture was stirred at 150° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate 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 added to a mixture of hydroxylammonium chloride (0.28 g), sodium hydrogen carbonate (0.40 g) and dimethyl sulfoxide (20 mL) previously stirred at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, and diluted with ethyl acetate. The mixture was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL), N,N′-carbonyldiimidazole (0.078 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 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 hydrogen sulfate 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 a colorless solid (0.12 g, 9%).

후처리

  1. stirringthe mixture was stirred at 150° C. for 16 hr
  2. washwashed with 5% aqueous potassium hydrogen sulfate solution
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue obtained by silica gel column chromatography
  6. stirringpreviously stirred at 40° C. for 30 min
  7. stirringThe reaction mixture was stirred at 90° C. for 16 hr
  8. washThe mixture was washed with water
  9. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  12. additionN,N′-carbonyldiimidazole (0.078 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 mL) were added
  13. stirringthe mixture was stirred at room temperature for 2 hr
  14. additionThe reaction mixture was diluted with ethyl acetate
  15. washwashed with saturated aqueous potassium hydrogen sulfate solution
  16. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  17. customThe solvent was evaporated under reduced pressure
  18. customthe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-3f72e58735f04785a432c214d5b04afa
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07803940B2

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