Methylamine → 6-Bromo-2-ethyl-3-methyl-3H-quinazolin-4-one

HRID 238201Notes

Reaction equation

HRID 238201 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:12][NH2:13].O.[C:15]1([CH3:25])C=CC(S(O)(=O)=O)=C[CH:16]=1.C(OCC)(OCC)(OCC)CC>CO>[Br:11][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[N:1]=[C:16]([CH2:15][CH3:25])[N:13]([CH3:12])[C:4]2=[O:6]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 66995Ethyl orthopropionateHCID 798582-Amino-5-bromobenzoic acidHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 599932916-Bromo-2-ethyl-3-methyl-3H-quinazolin-4-oneYield 39.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-amino-5-bromo-benzoic acid (10.00 g, 46.38 mmol) in methanol (25 mL) was added methylamine (100 ml of 2 M solution in methanol), p-toluenesulfonic acid monohydrate (8.82 g, 46.38 mmol), and triethyl orthopropionate (40.87 g, 231.9 mmol). The reaction was refluxed for 18 hours, at which time it was allowed to cool to room temperature. The solution was concentrated under reduced pressure. The residue was partitioned between sodium carbonate aqueous (50 ml) and dichloromethane (50 ml). The organic layer was then washed with saturated brine (2×30 ml). The combined organic phase was dried over magnesium sulfate and filtered. The solvent was removed under vacuum. The resulting residue was purified by silica gel chromatography with 100% dichloromethane. The product was collected and was dried under reduced pressure to give 6-Bromo-2-ethyl-3-methyl-3H-quinazolin-4-one (Yield 4.92 g, 39.9%). 1H NMR (400 MHz, CDCl3): □ 1.42 (t, 3H, J=7.33 Hz), 2.86 (dd, 2H, J=14.65, 7.58 Hz), 7.45 (d, 1H, J=8.5 Hz), 7.80 (dd, 1H, J=8.50, 2.02 Hz), 8.40 (d, 1H, J=2.05 Hz). MS m/z calc. 266.01, found (ESI); 267.0 (M+1)+. Retention time 2.44 minutes.

Workup

  1. temperatureThe reaction was refluxed for 18 hours, at which time it
  2. concentrationThe solution was concentrated under reduced pressure
  3. customThe residue was partitioned between sodium carbonate aqueous (50 ml) and dichloromethane (50 ml)
  4. washThe organic layer was then washed with saturated brine (2×30 ml)
  5. dry with materialThe combined organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed under vacuum
  8. customThe resulting residue was purified by silica gel chromatography with 100% dichloromethane
  9. customThe product was collected
  10. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-5538a82fb8af452bb3ea0baaa4750de5
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

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