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

HRID 591806Notes

Reaction equation

HRID 591806 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[CH3:8][C:9]1[CH:14]=[C:13]([C:15]2[NH:24][C:23](=[O:25])[C:22]3[C:17](=[CH:18][C:19](F)=[CH:20][C:21]=3[O:26][CH3:27])[N:16]=2)[CH:12]=[C:11]([CH3:29])[N:10]=1.O>CS(C)=O.C(O)(=O)C>[CH3:8][C:9]1[CH:14]=[C:13]([C:15]2[NH:24][C:23](=[O:25])[C:22]3[C:17](=[CH:18][C:19]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:20][C:21]=3[O:26][CH3:27])[N:16]=2)[CH:12]=[C:11]([CH3:29])[N:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 1363480402-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one

Product 1

HCID 1359390652-(2,6-Dimethylpyridin-4-yl)-5-methoxy-7-(2-methoxyethoxy)quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2-methoxyethanol (3 mL) in dimethyl sulfoxide (8 mL), sodium hydride (60% suspension in mineral oil, 0.40 g, 9.40 mmol) was added in portions and the reaction mixture was stirred at room temperature for 1 hour. To this reaction mixture was added 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-methoxy-3H-quinazolin-4-one (0.28 g, 0.94 mmol) and the reaction mixture was stirred at 90° C. for 16 hours. Water was added, acidified to pH approximately 4-5 with acetic acid, and the precipitated solid was filtered to give crude product, which was purified by preparative HPLC, to obtain the title compound as a white solid. Yield: 0.12 g (36%). MP 228.8-230.4° C. MS (ES) m/z: 356.05 (M++1). 1H NMR (400 MHz, CDCl3): δ 10.45 (s, 1H), 7.65 (s, 2H), 6.85 (d, J=1.6 Hz, 1H), 6.61 (d, J=1.6 Hz, 1H), 4.27 (t, J=4.8 Hz, 2H), 3.97 (s, 3H), 3.82 (t, J=4.8 Hz, 2H), 3.49 (s, 3H), 2.66 (s, 6H).

Workup

  1. stirringthe reaction mixture was stirred at 90° C. for 16 hours
  2. filtrationthe precipitated solid was filtered
  3. customto give crude product, which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-1dd3c47570a3403590a203fca60696f6
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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