Methanol → 2-(2,6-Dimethylpyridin-4-yl)-7-methoxy-5-(2-phenoxyethoxy)quinazolin-4(3H)-one

HRID 591822Notes

Reaction equation

HRID 591822 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12](F)=[CH:13][C:14]=3[O:19][CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:9]=2)[CH:5]=[C:4]([CH3:30])[N:3]=1.[CH3:31][O-:32].[Na+].CO.O>CN(C=O)C.C(O)(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:32][CH3:31])=[CH:13][C:14]=3[O:19][CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:9]=2)[CH:5]=[C:4]([CH3:30])[N:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 10942334Sodium MethoxideHCID 1363480192-(2,6-dimethylpyridin-4-yl)-7-fluoro-5-(2-phenoxyethoxy)-3H-quinazolin-4-one

Product 1

HCID 1359390702-(2,6-Dimethylpyridin-4-yl)-7-methoxy-5-(2-phenoxyethoxy)quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a suspension of 2-(2,6-dimethylpyridin-4-yl)-7-fluoro-5-(2-phenoxyethoxy)-3H-quinazolin-4-one (0.59 g, 1.45 mmol) in DMF (10 mL) was added a solution of sodium methoxide in methanol (25 wt %, 3.15 g, 14.5 mmol) and the reaction mixture was stirred at approximately 70-80° C. for 48 hours, then cooled to room temperature. Water (1 mL) was added, the mixture was neutralized to pH approximately 6-7 with acetic acid, concentrated, dissolved in DCM, washed with water and brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and the residue was passed through a column (eluted with 2% methanol in DCM), to give 0.12 g of the desired product. The crude product was washed with acetonitrile, then solubilized in dioxane, and precipitated by adding water to afford the title compound as a white solid. Yield: 70 mg (11%). 1H NMR (400 MHz, DMSO-d6): δ 12.08 (br s, 1H), 7.77 (s, 2H), 7.31 (t, J=7.81 Hz, 2H), 7.04 (d, J=8.20 Hz, 2H), 6.96 (t, J=7.42 Hz, 1H), 6.83 (d, J=1.56 Hz, 1H), 6.69 (s, 1H), 4.40-4.53 (m, 2H), 3.90 (s, 3H), 3.33 (s, 6H). MS (ES+) m/z: 418.14 (M+1)+; MP 172.3-173.2° C.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. dissolutiondissolved in DCM
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. washthe residue was passed through a column (eluted with 2% methanol in DCM)

Sources & evidence

ORD record
ord-f64230b0343547ec9dd2e9ab16c37a8e
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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