Water → HCID 135939075, compound

HRID 591831Notes

Reaction equation

HRID 591831 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:14][C:15]1[CH:20]=[C:19]([C:21]2[NH:30][C:29](=[O:31])[C:28]3[C:23](=[CH:24][C:25](F)=[CH:26][C:27]=3[O:32][CH3:33])[N:22]=2)[CH:18]=[C:17]([CH3:35])[N:16]=1.O>CS(C)=O.C(O)(=O)C>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:25]1[CH:24]=[C:23]2[C:28]([C:29](=[O:31])[NH:30][C:21]([C:19]3[CH:18]=[C:17]([CH3:35])[N:16]=[C:15]([CH3:14])[CH:20]=3)=[N:22]2)=[C:27]([O:32][CH3:33])[CH:26]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 121412-(Benzyloxy) ethanolHCID 24758Sodium hydrideHCID 1363480402-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one

Product 1

HCID 135939075HCID 135939075, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2-benzyloxy-ethanol (1.15 g, 10.0 mmol) in dimethyl sulfoxide (4 mL), sodium hydride (60% suspension in mineral oil, 0.20 g, 5.0 mmol) was added in portions and the reaction mixture was stirred at room temperature for 20 minutes. To this reaction mixture was added 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one (0.30 g, 1.0 mmol) and the reaction mixture was stirred at 85° C. for 24 hours. Water was added, and the mixture was acidified to pH approximately 4-5 with acetic acid and the precipitated solid was filtered to give crude product, which was purified by column chromatography (silica gel 230-400 mesh; eluting with hexane and ethyl acetate 10:1) to obtain the title compound as a white solid. Yield: 0.140 g (32.4%). MP 178-180° C. MS (ES) m/z: 432.18 (M++1). 1H NMR (400 MHz, CDCl3): δ 10.90 (s, 1H), 7.69 (s, 2H), 7.29-7.40 (m, 5H), 6.85 (d, J=2.0 Hz, 1H), 6.59 (d, J=2.0 Hz, 1H), 4.66 (s, 2H), 4.29 (m, 2H), 3.97 (s, 3H), 3.89 (m, 2H), 2.66 (s, 6H).

Workup

  1. stirringthe reaction mixture was stirred at 85° C. for 24 hours
  2. filtrationthe precipitated solid was filtered
  3. customto give crude product, which
  4. customwas purified by column chromatography (silica gel 230-400 mesh; eluting with hexane and ethyl acetate 10:1)

Sources & evidence

ORD record
ord-46c70faf523a433bafd4a8a01bdcf876
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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