Acetic Acid → HCID 135939071, compound

HRID 591824Notes

Reaction equation

HRID 591824 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][CH3:23])[N:9]=2)[CH:5]=[C:4]([CH3:25])[N:3]=1.C[O-].[Na+].CO.[C:31](O)(=[O:33])C>CN(C=O)C.O>[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:33][CH3:31])=[CH:13][C:14]=3[O:19][CH2:20][CH2:21][O:22][CH3:23])[N:9]=2)[CH:5]=[C:4]([CH3:25])[N:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 10942334Sodium MethoxideHCID 136348017HCID 136348017, compound

Product 1

HCID 135939071HCID 135939071, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 2-(2,6-dimethylpyridin-4-yl)-7-fluoro-5-(2-methoxyethoxy)-3H-quinazolin-4-one (0.42 g, 1.22 mmol) in DMF (10 mL) was added a solution of sodium methoxide in methanol (25 wt %, 2.8 g, 12.8 mmol) and the reaction mixture was stirred at 70° C. for 16 hours, then cooled to room temperature. Water (1 mL) was added, the mixture was neutralized to pH approximately 6 with acetic acid, diluted with water (50 mL), and extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo, to give 0.30 g of crude compound. Further purification by crystallization in acetone:Et2O (1:3) gave the title compound as a white solid. Yield: 91 mg (15%). 1H NMR (400 MHz, CDCl3): δ 10.08 (br s, 1H), 7.60 (br s, 2H), 6.87 (d, J=1.95 Hz, 2H), 6.55 (d, J=1.95 Hz, 2H), 4.25 (t, J=4.88 Hz, 2H), 3.93 (s, 3H), 3.83 (d, J=4.29 Hz, 2H), 3.44 (s, 3H), 2.64 (s, 6H). MS (ES+) m/z: 356.11 (M+1)+

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give 0.30 g of crude compound
  7. customFurther purification
  8. customby crystallization in acetone:Et2O (1:3)

Sources & evidence

ORD record
ord-4d69e411cbf546dfbd2c9152731523e4
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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