Magnesium trifluoromethanesulfonate → 6-(3-chlorophenyl)-4-cyclopropyl-4-methyl-3,4-dihydro-1H-quinazolin-2-one

HRID 2300091Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2300091
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14](CC2C=CC(OC)=CC=2)[C:13](=[O:27])[N:12]=[C:11]3[CH:28]2[CH2:30][CH2:29]2)[CH:5]=[CH:6][CH:7]=1.[O-]S([C:35](F)(F)F)(=O)=O.[Mg+2].[O-]S(C(F)(F)F)(=O)=O.C[Mg]Br>CCOCC>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13](=[O:27])[NH:12][C:11]3([CH:28]2[CH2:29][CH2:30]2)[CH3:35])[CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 2734125Magnesium trifluoromethanesulfonateHCID 98448416-(3-chlorophenyl)-4-cyclopropyl-1-(4-methoxybenzyl)-1H-quinazolin-2-oneHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 97968226-(3-chlorophenyl)-4-cyclopropyl-4-methyl-3,4-dihydro-1H-quinazolin-2-oneAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel2×

Versuchsvorschrift

To a solution of 6-(3-chlorophenyl)-4-cyclopropyl-1-(4-methoxybenzyl)-1H-quinazolin-2-one (0.25 g, 0.6 mmol) in anhydrous ether was added, at ambient temperature under nitrogen, magnesium triflate (0.78 g, 2.4 mmol). The mixture was stirred for 30 minutes and treated with a solution of methylmagnesium bromide in ether (3.0 M, 1.0 mL, 3.0 mmol). The reaction mixture was kept at room temperature under nitrogen for 3 hours and quenched with a mixture of a saturated aqueous ammonium chloride solution (10 mL) and 1N aqueous HCl solution (5 mL). The mixture was stirred at room temperature for 20 minutes and ethyl acetate (40 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine and dried (MgSO4). The solvent was removed and a half portion of the residue was dissolved in TFA (3 mL) and was stirred under nitrogen at room temperature for 72 hours. The solution was poured onto ice-water and the white precipitate obtained was collected on a filter. The solid was washed with water and then purified by a flash chromatography (methylene chloride:methanol/25:1, silica gel) to give 6-(3-chlorophenyl)-4-cyclopropyl-4-methyl-3,4-dihydro-1H-quinazolin-2-one as off-white solid(40 mg, 43%): mp 125-127° C.; 1H-NMR (DMSO-d6) δ 9.21 (s, 1H), 7.71 (s, 1H), 7.61 (d, 1H, J=7.8 Hz), 7.55 (d, 1H, J=1.6 Hz), 7.47 (dd, 1H, J=8.3, 1.8 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.36 (d, 1H, J=8.1 Hz), 6.84 (d, 1H, J=8.2 Hz), 6.79 (s, 1H), 1.54 (s, 3H), 1.11 (m, 1H), 0.42 (m, 1H), 0,15-0.20 (m, 3H); MS (ESI) m/z 313([M+H]+, 100%).

Aufarbeitung

  1. waitThe reaction mixture was kept at room temperature under nitrogen for 3 hours
  2. customquenched with a mixture of a saturated aqueous ammonium chloride solution (10 mL) and 1N aqueous HCl solution (5 mL)
  3. stirringThe mixture was stirred at room temperature for 20 minutes
  4. additionethyl acetate (40 mL) was added
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. customThe solvent was removed
  10. dissolutiona half portion of the residue was dissolved in TFA (3 mL)
  11. stirringwas stirred under nitrogen at room temperature for 72 hours
  12. additionThe solution was poured onto ice-water
  13. customthe white precipitate obtained
  14. customwas collected on a filter
  15. washThe solid was washed with water
  16. custompurified by a flash chromatography (methylene chloride:methanol/25:1, silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-a12d17b3b01548da9555244c1a058030
Quelldatensatz
uspto-grants-2002_12
Patentnummer
US06498154B1

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