Pyrrolidine → 5,7-Dimethoxy-2-(3-methyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)quinazolin-4(3H)-one
Reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:20][C:19](=[O:21])[C:18]3[C:13](=[CH:14][C:15]([O:24][CH3:25])=[CH:16][C:17]=3[O:22][CH3:23])[N:12]=2)=[CH:7][C:6]=1[CH3:26].[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>CN(C=O)C>[CH3:23][O:22][C:17]1[CH:16]=[C:15]([O:24][CH3:25])[CH:14]=[C:13]2[C:18]=1[C:19](=[O:21])[NH:20][C:11]([C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)=[C:6]([CH3:26])[CH:7]=1)=[N:12]2Participants
Procedure
To a suspension of 2-[4-(2-bromo-ethoxy)-3-methyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.70 g, 1.67 mmol) in anhydrous DMF (9 mL) was added pyrrolidine (0.55 mL, 6.68 mmol) and the reaction mixture was stirred at room temperature under nitrogen for 20 hours. Solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel 230-400 mesh; 9% methanol in dichloromethane as eluent) to give the title compound as an off-white solid. Yield: 0.62 g (90.6%). MP 230-231° C. 1H NMR (400 MHz, CDCl3): δ 9.96 (br s, 1H), 7.91-7.89 (m, 2H), 6.93 (d, J=7.6 Hz, 1H), 6.82 (d, J=2.4 Hz, 1H), 6.44 (d, J=2.4 Hz, 1H), 4.21 (t, J=6.0 Hz, 2H), 3.98 (s, 3H), 3.93 (s, 3H), 2.98 (t, J=6.0 Hz, 2H), 2.69 (br s, 4H), 2.32 (s, 3H), 1.84-1.81 (m, 4H). MS (ES−) m/z 408.13 (M−1, 100%), MS (ES+) m/z 410.14 (M+1, 75%).
Workup
- customSolvent was removed under reduced pressure
- customthe residue was purified by column chromatography (silica gel 230-400 mesh; 9% methanol in dichloromethane as eluent)
Sources & evidence
- ORD record
- ord-e1aa21a6e43f4135858e98d11912fc5b
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09238640B2
Reaction notes
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