Water → 7-(2-(Benzyloxy)ethoxy)-5-methoxy-2-(pyridin-4-yl)quinazolin-4(3H)-one
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+].F[C:15]1[CH:24]=[C:23]2[C:18]([C:19](=[O:31])[NH:20][C:21]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)=[N:22]2)=[C:17]([O:32][CH3:33])[CH:16]=1.O>CS(C)=O.C(O)(=O)C>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:15]1[CH:24]=[C:23]2[C:18]([C:19](=[O:31])[NH:20][C:21]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)=[N:22]2)=[C:17]([O:32][CH3:33])[CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 2-benzyloxy-ethanol (2 mL) in dimethyl sulfoxide (3 mL) was added sodium hydride (0.30 g, 7.4 mmol) in portions, and the reaction mixture was stirred at room temperature for 45 minutes. To this mixture was added 7-fluoro-5-methoxy-2-pyridin-4-yl-3H-quinazolin-4-one (0.20 g, 0.74 mmol) and the reaction mixture was heated at 80° C. for 16 hours. Water was added, the mixture was acidified with acetic acid to pH approximately 4-5, and the precipitated solid was filtered off, to obtain a crude product, which was purified by preparative HPLC to obtain the title compound as a light yellow solid. Yield: 0.12 g (40%). MP 228.2-229.9° C. 1H NMR (400 MHz, DMSO-d6): δ12.29 (s, 1H), 8.77 (d, 2H), 8.08 (d, 2H), 7.36 (m, 5H), 6.82 (s, 1H), 6.62 (s, 1H), 4.58 (s, 2H), 4.32 (t, 2H), 3.87 (s, 3H), 3.83 (t, 2H). MS (ES+) m/z: 404.51 (M+1).
Workup
- temperaturethe reaction mixture was heated at 80° C. for 16 hours
- filtrationthe precipitated solid was filtered off
- customto obtain a crude product, which
- customwas purified by preparative HPLC
Sources & evidence
- ORD record
- ord-fa6159f0496f4bfd8dbfc5c77de8cef5
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09238640B2
Reaction notes
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