Pyrrolidine → 5,7-Dichloro-2-(3,5-dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)quinazolin-4(3H)-one
Reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([Cl:24])=[CH:17][C:18]=3[Cl:23])[N:13]=2)=[CH:7][C:6]=1[CH3:25].[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>CN(C=O)C>[Cl:23][C:18]1[CH:17]=[C:16]([Cl:24])[CH:15]=[C:14]2[C:19]=1[C:20](=[O:22])[NH:21][C:12]([C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([O:4][CH2:3][CH2:2][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[C:6]([CH3:25])[CH:7]=1)=[N:13]2Participants
Procedure
To a solution of 2-[4-(2-bromo-ethoxy)-3,5-dimethylphenyl]-5,7-dichloro-3H-quinazolin-4-one (0.44 g, 1.00 mmol) in anhydrous DMF (10 mL) was added pyrrolidine (0.28 g, 4.00 mmol). The reaction mixture was stirred at room temperature for 6 hours under nitrogen. Solvent was evaporated under reduced pressure. Water (50 mL) was added. The separated solid was filtered, washed with water (20 mL), and dried under vacuum. The crude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and 5% methanol (containing 7.0 M ammonia) in CH2Cl2 as eluent) to give the title compound as a white solid. Yield: 0.31 g (72%). MP 209-210° C. 1H NMR (400 MHz, DMSO-d6): δ 12.39 (br s, 1H), 7.90 (s, 2H), 7.71 (d, J=1.95 Hz, 1H), 7.60 (d, J=1.95 Hz, 1H), 3.91 (t, J=5.85 Hz, 2H), 2.83 (t, J=6.05 Hz, 2H), 2.55 (m, 4H), 2.31 (s, 6H), 2.01 (m, 4H). MS (ES+) m/z 432.54 (100%), 434.49 (90%).
Workup
- customSolvent was evaporated under reduced pressure
- additionWater (50 mL) was added
- filtrationThe separated solid was filtered
- washwashed with water (20 mL)
- customdried under vacuum
- customThe crude compound was purified by the Simpliflash system (0-5% methanol in CH2Cl2 and 5% methanol (containing 7.0 M ammonia) in CH2Cl2 as eluent)
Sources & evidence
- ORD record
- ord-ea27d1b30ab14621ae6c9d6a6c7e6b5b
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09238640B2
Reaction notes
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