Water → 2-(2,6-Dimethylpyridin-4-yl)-7-(2-isopropoxyethoxy)-5-methoxyquinazolin-4(3H)-one

HRID 591828Notes

Reaction equation

HRID 591828 reaction equation
[H-].[Na+].[CH:3]([O:6][CH2:7][CH2:8][OH:9])([CH3:5])[CH3:4].[CH3:10][C:11]1[CH:16]=[C:15]([C:17]2[NH:26][C:25](=[O:27])[C:24]3[C:19](=[CH:20][C:21](F)=[CH:22][C:23]=3[O:28][CH3:29])[N:18]=2)[CH:14]=[C:13]([CH3:31])[N:12]=1.O>CS(C)=O>[CH3:10][C:11]1[CH:16]=[C:15]([C:17]2[NH:26][C:25](=[O:27])[C:24]3[C:19](=[CH:20][C:21]([O:9][CH2:8][CH2:7][O:6][CH:3]([CH3:5])[CH3:4])=[CH:22][C:23]=3[O:28][CH3:29])[N:18]=2)[CH:14]=[C:13]([CH3:31])[N:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7996IsopropylethanediolHCID 24758Sodium hydrideHCID 1363480402-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one

Product 1

HCID 1359390732-(2,6-Dimethylpyridin-4-yl)-7-(2-isopropoxyethoxy)-5-methoxyquinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a suspension of sodium hydride (60% suspension in mineral oil, 0.24 g, 6.00 mmol) in anhydrous DMSO (10 mL) was added 2-isopropoxy-ethanol at room temperature under nitrogen. The mixture was stirred for 20 minutes at room temperature, then 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one (0.30 g, 1.00 mmol) was added and the reaction mixture was stirred at 80° C. for 16 hours, then cooled to room temperature. Water (50 mL) was added, and the mixture was extracted with a mixture of ethyl acetate and THF (4:1, 200 mL). The organic phase was washed with brine and dried over anhydrous sodium sulfate. Solvent was evaporated, and the crude compound was purified by the Simpliflash system (3:15:82 methanol, ethyl acetate and dichloromethane as eluent) to give the title compound as a white solid. Yield: 127 mg (33%). MP 188-189° C. 1H NMR (400 MHz, CDCl3): δ 11.14 (br s, 1H), 7.72 (s, 2H), 6.86 (d, J=2.34 Hz, 1H), 6.59 (d, J=2.34 Hz, 1H), 4.35-4.15 (m, 2H), 3.97 (s, 3H), 3.89-3.79 (m, 2H), 3.78-3.64 (m, 1H), 2.66 (s, 6H), 1.23 (d, J=5.85 Hz, 6H). MS (ES+) m/z: 384.20 (100%).

Workup

  1. stirringthe reaction mixture was stirred at 80° C. for 16 hours
  2. temperaturecooled to room temperature
  3. extractionthe mixture was extracted with a mixture of ethyl acetate and THF (4:1, 200 mL)
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customSolvent was evaporated
  7. customthe crude compound was purified by the Simpliflash system (3:15:82 methanol, ethyl acetate and dichloromethane as eluent)

Sources & evidence

ORD record
ord-f6a9210b7945489aa66d15258aa55ab9
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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