Potassium Carbonate → 4-(3-Acetoxy-4-methylanilino)-6-methoxy-7-(4-pyridylmethoxy)quinazoline

HRID 1384517Notes

Reaction equation

HRID 1384517 reaction equation
Cl.[C:2]([O:5][C:6]1[CH:7]=[C:8]([CH:23]=[CH:24][C:25]=1[CH3:26])[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([OH:22])=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1)(=[O:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Br.Br[CH2:35][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=1>CN(C=O)C>[C:2]([O:5][C:6]1[CH:7]=[C:8]([CH:23]=[CH:24][C:25]=1[CH3:26])[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH2:35][C:36]3[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=3)=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][N:11]=1)(=[O:4])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 127522194-(Bromomethyl)pyridine hbrHCID 1356711804-(3-Acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 110373874-(3-Acetoxy-4-methylanilino)-6-methoxy-7-(4-pyridylmethoxy)quinazolineYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4-(3-acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (375 mg, 1 mmol) in DMF (16 ml ) were added at ambient temperature potassium carbonate (415 mg, 3 mmol) and 4-(bromomethyl)pyridine hydrobromide (J.Org.Chem. 1958, 23, 575, 278 mg, 1.1 mmol). The reaction mixture was heated at 60° C. for 2 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column flash chromatography, eluting with methylene chloride/methanol (95/5) to give 4-(3-acetoxy-4-methylanilino)-6-methoxy-7-(4-pyridylmethoxy)quinazoline (93 mg, 22%). m.p. 201-202° C. 1H NMR Spectrum: (DMSOd6) 2.12(s, 3H); 2.34(s, 3H); 4.02(s, 3H); 5.40(s, 2H); 7.27(s, 1H); 7.30(d, 1H); 7.51(d, 2H); 7.62(s, 1H); 7.65(d, 1H); 7.91(s, 1H); 8.47(s, 1H); 8.63(d, 2H); 9.53(s, 1H) MS−ESI: 453 [MNa]+, 431 [MH]+

Workup

  1. customThe mixture was evaporated
  2. customthe residue was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column flash chromatography
  7. washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-e65ef4379fde4514a39cb1f21b372dda
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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