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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 1718945
ノート
印刷プレビュー

反応式

HRID 1718945 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 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
収率 76%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-72cf13f96e944725934d29d401f8f849
出典データセット
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07803940B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート