Triphenylphosphine → 6-butyl-2-methyl-3-{4-[(2-methyltetrahydro-2H-pyran-4-yl)oxy]phenyl}-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one

HRID 1674281

Reaktionsgleichung

Reaktionsgleichung von HRID 1674281
[CH2:1]([C:5]1[N:10]=[C:9]([CH3:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[C:7](=[O:19])[C:6]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]2[NH:37][C:36](=[O:38])[O:35][N:34]=2)=[CH:23][CH:22]=1)[CH2:2][CH2:3][CH3:4].[CH3:39][CH:40]1[CH2:45][CH:44](O)[CH2:43][CH2:42][O:41]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.O>[CH2:1]([C:5]1[N:10]=[C:9]([CH3:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:44]3[CH2:43][CH2:42][O:41][CH:40]([CH3:39])[CH2:45]3)=[CH:14][CH:13]=2)[C:7](=[O:19])[C:6]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]2[NH:37][C:36](=[O:38])[O:35][N:34]=2)=[CH:23][CH:22]=1)[CH2:2][CH2:3][CH3:4]

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 100803792-Methyl-tetrahydro-pyran-4-OLHCID 1362033846-butyl-3-(4-hydroxyphenyl)-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one

Produkt 1

HCID 1361467156-butyl-2-methyl-3-{4-[(2-methyltetrahydro-2H-pyran-4-yl)oxy]phenyl}-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-oneAusbeute 60,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 6-butyl-3-(4-hydroxyphenyl)-2-methyl-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one (0.5 g), 2-methyltetrahydro-2H-pyran-4-ol (0.26 g) and triphenylphosphine (0.58 g) in tetrahydrofuran (5 mL) was added dropwise diisopropyl azodicarboxylate (1.9 M toluene solution, 1.2 mL). After stirring for 2 hr, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and a mixture of the residue, hydroxylammonium chloride (0.77 g), sodium hydrogen carbonate (1.1 g) and dimethyl sulfoxide (10 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 (10 mL). N,N′-carbonyldiimidazole (0.27 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added, and the mixture was stirred at room temperature for 30 min. 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 (0.36 g, 53%) as an amorphous solid.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. additiona mixture of the residue, hydroxylammonium chloride (0.77 g), sodium hydrogen carbonate (1.1 g) and dimethyl sulfoxide (10 mL)
  6. stirringwas stirred overnight at 90° C
  7. additionThe reaction mixture was diluted with ethyl acetate
  8. washwashed 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 (10 mL)
  12. additionN,N′-carbonyldiimidazole (0.27 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added
  13. stirringthe mixture was stirred at room temperature for 30 min
  14. additionThe reaction mixture was diluted with ethyl acetate
  15. washwashed with 5% 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

Quellen und Nachweise

ORD-Eintrag
ord-e066d0c6615e497cb9b14189930b99b1
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07998968B2

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