Ammonium formate → 5-hydroxy-2-(4-hydroxy-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-one

HRID 1498768Notes

Reaction equation

HRID 1498768 reaction equation
C([O-])=O.[NH4+].C([O:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]([O:32][CH3:33])=[CH:25][C:26]=3[OH:31])[N:21]=2)=[CH:15][C:14]=1[CH3:34])C1C=CC=CC=1>CN(C=O)C.[C].[Pd]>[OH:31][C:26]1[CH:25]=[C:24]([O:32][CH3:33])[CH:23]=[C:22]2[C:27]=1[C:28](=[O:30])[NH:29][C:20]([C:16]1[CH:17]=[C:18]([CH3:19])[C:13]([OH:12])=[C:14]([CH3:34])[CH:15]=1)=[N:21]2

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 1363988572-(4-benzyloxy-3,5-dimethyl-phenyl)-5-hydroxy-7-methoxy-3H-quinazolin-4-one

Product 1

HCID 1360379705-hydroxy-2-(4-hydroxy-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-oneYield 74%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-(4-benzyloxy-3,5-dimethyl-phenyl)-5,7-dimethoxy-3H-quinazolin-4-one (1.2 g, 2.92 mmol) and magnesium bromide (0.644 g, 3.5 mmol) in pyridine (50 mL) was stirred at reflux for 12 h. The mixture was concentrated and the solid residue was made into slurry with HCl (2 N, 100 mL). The solid was collected by filtration, washed with water and hexanes to yield 2-(4-benzyloxy-3,5-dimethyl-phenyl)-5-hydroxy-7-methoxy-3H-quinazolin-4-one as a white solid (0.76 g, 65%). A solution of ammonium formate (0.945 g, 15 mmol) and 2-(4-benzyloxy-3,5-dimethyl-phenyl)-5-hydroxy-7-methoxy-3H-quinazolin-4-one (0.1 g, 0.25 mmol) in DMF (50 mL) was mixed with palladium carbon (0.1 g) and stirred at 85° C. for 14 h. The resulting suspension was cooled to room temperature, passed through a Celite pad, and washed with DCM. The filtrate was concentrated and the residue was diluted with water (20 mL). The resulting solid was collected by filtration and washed with hexanes to afford 5-hydroxy-2-(4-hydroxy-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-one (57 mg, 74%) as light yellow solid. Selected data: MS (ES) m/z: 312.94; MP 291.3-293° C.

Workup

  1. temperatureThe resulting suspension was cooled to room temperature
  2. washwashed with DCM
  3. concentrationThe filtrate was concentrated
  4. additionthe residue was diluted with water (20 mL)
  5. filtrationThe resulting solid was collected by filtration
  6. washwashed with hexanes

Sources & evidence

ORD record
ord-6558ed960a9c40bd84713a2c2b82eea4
Source dataset
uspto-grants-2015_12
Patent number
US09199990B2

Reaction notes

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