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

HRID 2300090Notes

Reaction equation

HRID 2300090 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.[K].[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=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]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([O:24][CH3:23])=[CH:26][CH:27]=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

5

Reactant 3

HCID 699934-Methyloxybenzyl chlorideHCID 5462222PotassiumHCID 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 hexmethylsilyl 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 ammoniun 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 ammoniun 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-d1125536cdcf4aa8903ec018f5dd6fd3
Source dataset
uspto-grants-2002_12
Patent number
US06498154B1

Reaction notes

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