Water → 4-(4-Fluorophenyl)-7-(morpholin-4-ylmethyl)quinoline-2-carboxamide
Reaction equation
Br[CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:8][C:9]([C:13]#[N:14])=[N:10]2)=[CH:5][CH:4]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.[OH-:28].[Na+].O>C(#N)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:7]2[C:6]3[C:11](=[CH:12][C:3]([CH2:2][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:4][CH:5]=3)[N:10]=[C:9]([C:13]([NH2:14])=[O:28])[CH:8]=2)=[CH:16][CH:17]=1Participants
Conditions
- Temperature
- 50 °C
Procedure
To a room temperature solution of 7-(bromomethyl)-4-(4-fluorophenyl)quinoline-2-carbonitrile (2-1, 311.0 mg, 0.895 mmol, 1.0 equiv.) in acetonitrile (10.0 mL) was added morphline (85.77 mg, 0.985 mmol, 1.1 equiv.) and 5.0 M aqueous NaOH (2.69 mL, 13.43 mmol, 15 equiv.), and the resulting mixture was stirred at 50° C. for 4 days. After cooling to room temperature, water (100.0 mL) was added and the mixture was stirred for 30 minutes. A yellow solid was collected via suction filtration, washed with water, dried in vacuo. The solid was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 4-(4-fluorophenyl)-7-(morpholin-4-ylmethyl)quinoline-2-carboxamide (4-1, 291.0 mg, 80.0%) as a colorless solid. 1H NMR (500 MHz, CDCl3): δ 8.216 (s, 1H); 8.098 (br s, 2H); 7.911 (d, J=8.54 Hz, 1H); 7.642 (d, J=8.55 Hz, 1H); 7.503-7.529 (m, 2H); 7.219-7.263 (m, 2H); 5.798 (br s, 1H); 3.734 (br s, 6H); 2.528 (br s, 2H). LRMS m/z (M+H)+ 366.2 found, 366.2 required.
Workup
- temperatureAfter cooling to room temperature
- stirringthe mixture was stirred for 30 minutes
- filtrationA yellow solid was collected via suction filtration
- washwashed with water
- customdried in vacuo
- customThe solid was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)
Sources & evidence
- ORD record
- ord-f1b8ad40176646839dfd377f439b5813
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09278960B2
Reaction notes
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