Methyl iodide → (7-Chloro-3,6-dimethyl-4-oxo-3,4-dihydroquinazolin-2-yl)methyl acetate

HRID 47851Notes

Reaction equation

HRID 47851 reaction equation
[C:1]([O:4][CH2:5][C:6]1[NH:15][C:14](=[O:16])[C:13]2[C:8](=[CH:9][C:10]([Cl:18])=[C:11]([CH3:17])[CH:12]=2)[N:7]=1)(=[O:3])[CH3:2].[H-].[Na+].I[CH3:22]>CN(C=O)C.ClCCl>[C:1]([O:4][CH2:5][C:6]1[N:15]([CH3:22])[C:14](=[O:16])[C:13]2[C:8](=[CH:9][C:10]([Cl:18])=[C:11]([CH3:17])[CH:12]=2)[N:7]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 1354321952-Acetoxymethyl-7-chloro-6-methyl-3,4-dihydroquinazolin-4-one

Product 1

HCID 11033278(7-Chloro-3,6-dimethyl-4-oxo-3,4-dihydroquinazolin-2-yl)methyl acetateYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-acetoxymethyl-7-chloro-6-methyl-3,4-dihydroquinazolin-4-one 0.428 g, 1.6 mmol) in anhydrous DMF (13 ml) was added sodium hydride (60% dispersion, 0.070 g, 1.76 mmol) under argon. Stirring was continued at room temperature for 1 min and then iodomethane (0.20 ml, 3.2 mmol) was added into the reaction mixture with a syringe via a septum. Stirring was continued at room temperature for 1 hour and the reaction mixture was then partitioned between ethyl acetate (130 ml) and brine (80 ml). The organic layer was washed with dilute brine (80 ml), dried (Na2SO4) and concentrated in vacuo to leave an orange residue. This orange residue was dissolved in dichloromethane and to this solution silica gel (Art 7734, 1.7 g) was added. The solvent was removed in vacuo and the orange free running powder was placed on a silica gel column made up in 5% ethyl acetate in dichloromethane. The column was eluted with 5% ethyl acetate in dichloromethane to afford a pale yellow solid (0.300 g, 67%), mp 110-112° C.; 1H-NMR (DMSO-d6) 2.17 (s, 3H, CH3CO), 2.47 (s, 3H, 6-CH3), 3.54 (s, 3H, N3—CH3), 5.23 (s, 2H, 2-CH2O), 7.71, 8.09 (2×s, 2H, 5-H, 8-H).

Workup

  1. stirringStirring
  2. waitwas continued at room temperature for 1 hour
  3. customthe reaction mixture was then partitioned between ethyl acetate (130 ml) and brine (80 ml)
  4. washThe organic layer was washed with dilute brine (80 ml)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto leave an orange residue
  8. additionwas added
  9. customThe solvent was removed in vacuo
  10. washThe column was eluted with 5% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-84a8e5fed2fb490d8ce2ef8616120707
Source dataset
uspto-grants-2004_03
Patent number
US06699861B1

Reaction notes

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