Hydrochloric Acid → 4-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamine
Reaction equation
[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.Cl>CO>[CH3:16][O:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[O:17][CH3:18])[N:8]=[CH:7][CH:6]=[C:5]2[O:4][C:3]1[CH:19]=[CH:20][C:21]([NH2:23])=[CH:22][C:2]=1[F:1]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of A1 (230 mg, 0.67 mmol, 1.0 eq.) in MeOH (50 mL) Pd/C (10% w/w, 23 mg) and aq. HCl-solution (1N, 1.34 mL, 2.0 eq.) were added. The reaction mixture was stirred under hydrogen atmosphere (1 atm) at RT for 48 h. The suspension was filtered through a pad of Celite®. The solvent was removed in vacuo and the crude product was purified using an Isolute® SPE column SCX, loading the reaction mixture as a MeOH solution and then eluting the desired compound with 2N NH3 in MeOH. The title compound A2 was isolated after evaporation of the solvent under reduced pressure as a white solid (200 mg, 0.64 mmol, 95%). 1H NMR (400 MHz, d6-DMSO, 300K) δ 3.92 (s, 6H), 4.97 (br s, 2H), 6.38 (d, J=5.3 Hz, 1H), 6.45 (dd, J=2.4 Hz, J=8.5 Hz, 1H), 6.53 (dd, J=2.4 Hz, J=13.2 Hz, 1H), 7.05 (t, J=9.0 Hz, 1H), 7.36 (s, 1H), 7.49 (s, 1H), 8.44 (d, J=5.3 Hz, 1H). MS (ES) C17H16FN2O3 requires: 314. Found: 315 (M+H)+.
Workup
- additionwere added
- filtrationThe suspension was filtered through a pad of Celite®
- customThe solvent was removed in vacuo
- customthe crude product was purified
- washeluting the desired compound with 2N NH3 in MeOH
Sources & evidence
- ORD record
- ord-fea2c48bb08442989304958ff616cc9e
- Source dataset
- uspto-grants-2015_04
- Patent number
- US08999982B2
Reaction notes
Loading…