Pyrrolidine → 5,7-Dimethoxy-2-(3-methoxy-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)quinazolin-4(3H)-one
Reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:13]2[NH:22][C:21](=[O:23])[C:20]3[C:15](=[CH:16][C:17]([O:26][CH3:27])=[CH:18][C:19]=3[O:24][CH3:25])[N:14]=2)[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>C1COCC1>[CH3:25][O:24][C:19]1[CH:18]=[C:17]([O:26][CH3:27])[CH:16]=[C:15]2[C:20]=1[C:21](=[O:23])[NH:22][C:13]([C:7]1[CH:6]=[C:5]([O:4][CH2:3][CH2:2][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=1)=[N:14]2Participants
Procedure
To a solution of 2-[3-(2-bromo-ethoxy)-5-methoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (7.10 g, 16.0 mmol) in THF (20 mL) was added pyrrolidine (11.38 g, 160.0 mmol) and the reaction mixture was stirred at room temperature for 15 hours. THF was removed under reduced pressure, the residue was purified by column chromatography (silica gel 230-400 mesh; eluting with 5% 2.0 M ammonia in methanol solution in dichloromethane) to give the title compound as a white solid. Yield: 3.2 g (47%). MP 159-160° C. 1H NMR (400 MHz, CDCl3): δ 10.66 (s, 1H), 7.25 (m, 2H), 6.84 (d, J=2.0 Hz, 1H), 6.67 (t, J=2.4 Hz, 1H), 6.45 (d, J=2.0 Hz, 1H), 4.21 (t, J=6.0 Hz, 2H), 3.95 (s, 3H), 3.93 (s, 3H), 3.89 (s, 3H), 2.93 (t, J=6.0 Hz, 2H), 2.64 (m, 4H), 1.80 (m, 4H). MS (ES+) m/z: 426.20 (M+1).
Workup
- customTHF was removed under reduced pressure
- customthe residue was purified by column chromatography (silica gel 230-400 mesh; eluting with 5% 2.0 M ammonia in methanol solution in dichloromethane)
Sources & evidence
- ORD record
- ord-c2b0b58d11cd4a769a9b212dca1ab8a4
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09238640B2
Reaction notes
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