Hydrochloric Acid → 1-(3-(1-(5,7-Difluoroquinolin-6-yl)ethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone
Reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([CH:15]([C:17]3[C:18]([F:28])=[C:19]4[C:24](=[CH:25][C:26]=3[F:27])[N:23]=[CH:22][CH:21]=[CH:20]4)[CH3:16])=[N:13][N:14]=2)[N:11]=1)=[CH2:5])C.Cl>CC(O)=O>[F:28][C:18]1[C:17]([CH:15]([C:12]2[N:10]3[N:11]=[C:6]([C:4](=[O:3])[CH3:5])[CH:7]=[CH:8][C:9]3=[N:14][N:13]=2)[CH3:16])=[C:26]([F:27])[CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][CH:22]=[N:23]2Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
The crude 6-{1-[6-(1-ethoxy-vinyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]-ethyl}-5,7-difluoro-quinoline obtained from the previous step was dissolved in HOAc (50 mL), 3N HCl aqueous solution (5 mL) was added. The reaction mixture was stirred at rt overnight. LC/MS showed the reaction was complete. Solvent was removed under reduced pressure. EtOAc was added, and cold 1N NaOH aqueous solution was added slowly until pH 8-9. The mixture was extracted with EtOAc, and the combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and purified by column chromatography to afford 1.0 g (65% for two steps) of the title compound as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.92 (dd, 1H), 8.32 (d, 1H), 8.14 (d, 1H), 7.68 (d, 1H), 7.61 (d, 1H), 7.42 (dd, 1H), 5.32 (q, 1H), 2.43 (s, 3H), 2.21 (d, 3H). LCMS (method A): [MH]+=354, tR=4.42 min.
Workup
- customSolvent was removed under reduced pressure
- additionEtOAc was added
- additioncold 1N NaOH aqueous solution was added slowly until pH 8-9
- extractionThe mixture was extracted with EtOAc
- dry with materialthe combined organic layers were dried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated
- custompurified by column chromatography
Sources & evidence
- ORD record
- ord-e209ee3e364e449eb2c9979b88f8e758
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08507676B2
Reaction notes
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