Methyl iodide → 3-(3-bromo-2-methylphenyl)-8-chloro-1-methylquinazoline-2,4(1H,3H)-dione

HRID 523213Notes

Reaction equation

HRID 523213 reaction equation
[Br:1][C:2]1[C:3]([CH3:21])=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]([Cl:19])[CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]2=[O:20])[CH:5]=[CH:6][CH:7]=1.[C:22]([O-])([O-])=O.[Cs+].[Cs+].IC.CCOC(C)=O>CN(C=O)C.O>[Br:1][C:2]1[C:3]([CH3:21])=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]([Cl:19])[CH:13]=[CH:14][CH:15]=3)[N:10]([CH3:22])[C:9]2=[O:20])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 1177608883-(3-bromo-2-methylphenyl)-8-chloroquinazoline-2,4(1H,3H)-dione

Product 1

HCID 1177611623-(3-bromo-2-methylphenyl)-8-chloro-1-methylquinazoline-2,4(1H,3H)-dioneYield 86.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(3-bromo-2-methylphenyl)-8-chloroquinazoline-2,4(1H,3H)-dione (1.45 g, 3.97 mmol) in DMF (15 mL) was treated with Cs2CO3 (3.88 g, 11.9 mmol) and iodomethane (2.48 mL, 39.7 mmol) and stirred at room temperature for 1.5 h. The mixture was diluted with water and a mixture of EtOAc and hexanes. The organic phase was washed with water, dried and concentrated. The residue was purified by column chromatography on silica gel (80 g), eluting with EtOAc-hexanes (gradient from 5-40%), to give 3-(3-bromo-2-methylphenyl)-8-chloro-1-methylquinazoline-2,4(1H,3H)-dione as a white solid (1.3 g, 81% yield). Mass spectrum m/z 379, 391 (M+H)+.

Workup

  1. washThe organic phase was washed with water
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography on silica gel (80 g)
  5. washeluting with EtOAc-hexanes (gradient from 5-40%)

Sources & evidence

ORD record
ord-05bff8c484ce4b2385cc4486ddb168ab
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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