Methyl iodide → 3-(3-Bromo-2-methylphenyl)-8-fluoro-1-methyl-1,2,3,4-tetrahydroquinazoline-2,4-dione

HRID 523201Notes

Reaction equation

HRID 523201 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]([F: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>CN(C=O)C.CCOC(C)=O.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]([F: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 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 1177612023-(3-bromo-2-methylphenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione2×

Product 1

HCID 1177612173-(3-Bromo-2-methylphenyl)-8-fluoro-1-methyl-1,2,3,4-tetrahydroquinazoline-2,4-dioneYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(3-bromo-2-methylphenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione [Intermediate 1] (4.80 g, 13.8 mmol) in DMF (25 mL) was treated with Cs2CO3 (13.4 g, 41.2 mmol). The suspension was stirred at room temperature and treated dropwise (but quickly) with iodomethane (4.30 mL, 68.7 mmol) and stirred rapidly at room temperature for 1 h. The mixture was diluted with EtOAc and water (200 mL). The organic phase was separated and washed sequentially with water and brine, then was dried and concentrated to provide 3-(3-bromo-2-methylphenyl)-8-fluoro-1-methylquinazoline-2,4(1H,3H)-dione as a tan glassy foam (4.80 g, 96% yield). Mass spectrum m/z 363, 365 (M+H)+.

Workup

  1. stirringstirred rapidly at room temperature for 1 h
  2. customThe organic phase was separated
  3. washwashed sequentially with water and brine
  4. customwas dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-be6225d7e2344b328f9a54ec8ac95f4b
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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