Hydrochloric Acid → 6-(6-Ethoxy-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline
Reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.[OH-].[Na+].Cl.[CH3:25][CH2:26][OH:27]>>[CH2:26]([O:27][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1)[CH3:25]Participants
Conditions
- Temperature
- 80 °C
Procedure
6-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Example 14, 112 mg, 0.380 mmol) was suspended in EtOH (1 mL). 2 M NaOH (950 μL, 1.900 mmol) was added and the RM was stirred at 80° C. for 1 h. The mixture was neutralized with 2 M HCl until pH=6 and then concentrated. The residue was diluted with DCM and the obtained solution was dried over Na2SO4, filtered and concentrated. The residue was crystallized in Et2O and small amount of isopropanol. The resulting solid was purified by flash chromatography (Flashmaster, with a 20 g silica gel column, TBME/MeOH: 100:0→85:15) and crystallized again in Et2O to afford the title compound as a yellow solid (tR 1.67 min (conditions 6), MH+=305.2, 1H-NMR in DMSO-d6: 8.85 (m, 1H); 8.30 (m, 1H); 7.95 (m, 2H); 7.89 (m, 1H); 7.75 (m, 1H); 7.56 (s, 1H); 7.50 (dd, 1H); 6.80 (d, 1H); 4.44 (s, 2H); 4.35 (q, 2H); 1.31 (t, 3H)).
Workup
- concentrationconcentrated
- additionThe residue was diluted with DCM
- dry with materialthe obtained solution was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was crystallized in Et2O
- customThe resulting solid was purified by flash chromatography (Flashmaster
- customwith a 20 g silica gel column, TBME/MeOH: 100:0→85:15) and crystallized again in Et2O
Sources & evidence
- ORD record
- ord-3a5aabf779254660946057a596122487
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822468B2
Reaction notes
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