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2,6-Lutidine → 2-ethyl-3-(4-{[1-(hydroxymethyl)cyclobutyl]oxy}phenyl)-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one

HRID 1674275
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HRID 1674275 반응식
[CH2:1]([C:3]1[N:4]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3([CH2:39][OH:40])[CH2:38][CH2:37][CH2:36]3)=[CH:30][CH:29]=2)[C:5](=[O:27])[C:6]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=1)[CH3:2].[N:41]1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C(C)(C)C)(C)C)(=O)=O.[C:64]([O:67]CC)(=[O:66])C>ClCCl>[CH2:1]([C:3]1[N:4]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3([CH2:39][OH:40])[CH2:36][CH2:37][CH2:38]3)=[CH:30][CH:29]=2)[C:5](=[O:27])[C:6]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]3[NH:41][C:64](=[O:66])[O:67][N:26]=3)=[CH:17][CH:18]=2)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=1)[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 79372,6-LutidineHCID 8857Ethyl AcetateHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 574609254'-{[2-Ethyl-1-(4-{[1-(hydroxymethyl)cyclobutyl]oxy}phenyl)-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile

생성물 1

HCID 136146914
2-ethyl-3-(4-{[1-(hydroxymethyl)cyclobutyl]oxy}phenyl)-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one
수율 76%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 4′-{[2-ethyl-1-(4-{[1-(hydroxymethyl)cyclobutyl]oxy}phenyl)-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.5 g) and 2,6-lutidine (0.17 mL) in dichloromethane (5 mL) was added tert-butyl(dimethyl)silyl trifluoromethanesulfonate (0.34 mL) at 0° C., and the mixture was stirred overnight. 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. A mixture of the residue, hydroxylammonium chloride (0.67 g), sodium hydrogen carbonate (0.97 g) and dimethyl sulfoxide (5 mL) was stirred overnight at 90° C. The reaction mixture was diluted with ethyl acetate, 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 (5 mL). N,N′-carbonyldiimidazole (0.23 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 mL) were added, and the mixture was stirred at room temperature for 30 min. Tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 1.9 mL) was added, and the mixture was stirred overnight at 50° C. 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 and the residue was purified by silica gel column chromatography to give the title compound (0.43 g, 76%) as an amorphous solid.

후처리

  1. washwashed with 5% aqueous potassium hydrogen sulfate solution
  2. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. additionA mixture of the residue, hydroxylammonium chloride (0.67 g), sodium hydrogen carbonate (0.97 g) and dimethyl sulfoxide (5 mL)
  5. stirringwas stirred overnight at 90° C
  6. additionThe reaction mixture was diluted with ethyl acetate
  7. washwashed 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 (5 mL)
  11. additionN,N′-carbonyldiimidazole (0.23 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 mL) were added
  12. stirringthe mixture was stirred at room temperature for 30 min
  13. additionTetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 1.9 mL) was added
  14. stirringthe mixture was stirred overnight at 50° C
  15. additionThe reaction mixture was diluted with ethyl acetate
  16. washwashed with 5% aqueous potassium hydrogen sulfate solution
  17. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. customthe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-e09b28a9bd954351b9c82fa2a591a8a0
출처 데이터셋
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07998968B2

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