4-Methyloxybenzyl chloride → 6-(3-chlorophenyl)-4-cyclopropyl-1-(4-methoxybenzyl)-1H-quinazolin-2-one

HRID 277843Notes

Reaction equation

HRID 277843 reaction equation
[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:18])[N:12]=[C:11]3[CH:19]2[CH2:21][CH2:20]2)[CH:5]=[CH:6][CH:7]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1>CN(C=O)C>[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]([CH2:28][C:27]2[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=2)[C:13](=[O:18])[N:12]=[C:11]3[CH:19]2[CH2:21][CH2:20]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 699934-Methyloxybenzyl chlorideHCID 178517394HCID 178517394, compound

Product 1

HCID 98448416-(3-chlorophenyl)-4-cyclopropyl-1-(4-methoxybenzyl)-1H-quinazolin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 6-(3-chlorophenyl)-4-cyclopropyl-1H-quinazolin-2-one (0.5 g, 1.68 mmol) in anhydrous DMF was added potassium hexamethylsilyl amide (0.45 g, 2.1 mmol) at ambient temperature under nitrogen. The reaction mixture was stirred at ambient temperature for 30 minutes, treated with p-methoxy benzyl chloride (0.35 mL, 2.5 mmol), and heated at 55° C. for 5 hours. The mixture was then cooled to room temperature and quenched with a saturated aqueous ammonium chloride solution (10 mL). Methylene chloride (50 mL) was added and organic layer was separated. The aqueous layer was extracted with methylene chloride (2×20 mL) and the combined organic layers were washed with brine and dried (MgSO4). After removal of solvent, the residue was separated on a flash chromatography (silica gel, hexane:ethyl acetate/1:1) to afford 6-(3-chlorophenyl)-4-cyclopropyl-1-(4-methoxybenzyl)-1H-quinazolin-2-one as an off-white solid: mp 173-174° C.; 1H-NMR (DMSO-d6) δ 8.65 (d, 1H, J=1.8 Hz), 8.10 (dd, 1H, J=8.9, 1.8 Hz), 7.93 (d, 1H, J=1.6 Hz), 7.79 (d, 1H, J=7.6 Hz), 7.53 (d, 2H, J=8.4 Hz), 7.46 (t, 1H, J=8.1 Hz), 7.21 (d, 2H, J=8.6 Hz), 6.88 (d, 2H, J=8.6 Hz), 5.41 (s, 2H), 3.73 (s, 3H), 3.18 (m, 1H), 1.18-1.27 (m, 4H); MS (CI) m/z 417([M+H]+, 100%); Anal. Calc. For C25H21ClN2O2: C, 72.02, H, 5.08, N, 6.72. Found: C, 71.88, H, 4.91, N, 6.70.

Workup

  1. temperatureheated at 55° C. for 5 hours
  2. temperatureThe mixture was then cooled to room temperature
  3. customquenched with a saturated aqueous ammonium chloride solution (10 mL)
  4. additionMethylene chloride (50 mL) was added
  5. customorganic layer was separated
  6. extractionThe aqueous layer was extracted with methylene chloride (2×20 mL)
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. customAfter removal of solvent
  10. customthe residue was separated on a flash chromatography (silica gel, hexane:ethyl acetate/1:1)

Sources & evidence

ORD record
ord-4ee876cf5294404d997158dccb8c66b3
Source dataset
uspto-grants-2002_03
Patent number
US06358948B1

Reaction notes

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