2-Methoxyethanol → HCID 136348032, compound

HRID 591837Notes

Reaction equation

HRID 591837 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].F[C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:26])[NH:14][C:15]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[CH:20]=3)=[N:16]2)=[C:11]([O:27][CH3:28])[CH:10]=1>CS(C)=O.CCOCC>[CH3:28][O:27][C:11]1[CH:10]=[C:9]([O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:18]=[C:17]2[C:12]=1[C:13](=[O:26])[NH:14][C:15]([C:19]1[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[CH:20]=1)=[N:16]2

Participants

6

Reactant 3

HCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 136348057HCID 136348057, compound

Product 1

HCID 136348032HCID 136348032, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-methoxy-ethanol (0.64 g, 8.40 mmol) in anhydrous DMSO (4 mL) was added sodium hydride (60% suspension in mineral oil, 0.12 g, 5.00 mmol) in small portions and the reaction mixture was stirred at room temperature for 30 minutes. To this mixture was added a solution of 7-fluoro-5-methoxy-2-(2-methyl-pyridin-4-yl)-3H-quinazolin-4-one (0.24 g, 0.84 mmol) in anhydrous DMSO (12 mL). The reaction mixture was stirred at 80° C. for 3 hours, then cooled to room temperature, and diluted with ether (500 mL). The solid was filtered and washed with ether. The crude compound was purified by column chromatography (silica gel 230-400 mesh; 4% methanol in dichloromethane). The compound was further purified by preparative HPLC to give the title compound as a white solid. Yield: 60 mg (21%). MP 260-262° C. 1H NMR (400 MHz, DMSO-d6): δ 8.62 (d, J=5.07 Hz, 1H), 7.98 (s, 1H), 7.88 (d, J=5.07 Hz, 1H), 6.80 (d, J=2.34 Hz, 1H), 6.61 (d, J=2.34 Hz, 1H), 4.25 (t, J=4.68 Hz, 2H), 3.86 (s, 3H), 3.71 (t, J=3.90 Hz, 2H), 3.33 (s, 3H), 2.57 (s, 3H). MS (ES) m/z: 342.07 (M+1) (100%).

Workup

  1. stirringThe reaction mixture was stirred at 80° C. for 3 hours
  2. temperaturecooled to room temperature
  3. filtrationThe solid was filtered
  4. washwashed with ether
  5. customThe crude compound was purified by column chromatography (silica gel 230-400 mesh; 4% methanol in dichloromethane)
  6. customThe compound was further purified by preparative HPLC

Sources & evidence

ORD record
ord-6b74c15e8edd44b092bd7125a880ecdc
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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