Methyl iodide → 3-(3-Bromo-2-methylphenyl)-8-methoxy-1-methylquinazoline-2,4-dione

HRID 523219Notes

Reaction equation

HRID 523219 reaction equation
[Br:1][C:2]1[C:3]([CH3:22])=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]([O:19][CH3:20])[CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]2=[O:21])[CH:5]=[CH:6][CH:7]=1.IC.[C:25]([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1>[Br:1][C:2]1[C:3]([CH3:22])=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]([O:19][CH3:20])[CH:13]=[CH:14][CH:15]=3)[N:10]([CH3:25])[C:9]2=[O:21])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 1177606713-(3-bromo-2-methylphenyl)-8-methoxyquinazoline-2,4(1H,3H)-dione

Product 1

HCID 1177612063-(3-Bromo-2-methylphenyl)-8-methoxy-1-methylquinazoline-2,4-dioneYield 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(3-bromo-2-methylphenyl)-8-methoxyquinazoline-2,4(1H,3H)-dione (535 mg, 1.48 mmol), iodomethane (0.185 mL, 2.96 mmol) and Cs2CO3 (965 mg, 2.96 mmol) in THF (20 mL) was stirred at room temperature overnight. The mixture was filtered and concentrated. The residue was dissolved in DCM, washed sequentially with saturated aqueous NaHCO3 and water, dried and concentrated. The residue was purified by column chromatography on silica gel (40 g silica), eluting with EtOAc-hexanes (gradient from 0-100%), to give 3-(3-bromo-2-methylphenyl)-8-methoxy-1-methylquinazoline-2,4(1H,3H)-dione (442 mg). Mass spectrum m/z 375, 377 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 7.90 (dd, J=7.2, 2.3 Hz, 1H), 7.66 (dd, J=8.0, 1.2 Hz, 1H), 7.31-7.22 (m, 2H), 7.22-7.19 (m, 1H), 7.17-7.13 (m, 1H), 3.97 (s, 3H), 3.89 (s, 3H), 2.23 (s, 3H).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in DCM
  4. washwashed sequentially with saturated aqueous NaHCO3 and water
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (40 g silica)
  8. washeluting with EtOAc-hexanes (gradient from 0-100%)

Sources & evidence

ORD record
ord-b0429b8a53fa4de380b40d88e53e87c8
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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