Methanesulfonic Acid → 6-(Difluoro(6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo(4,3-b)pyridazin-3-yl)methyl)quinoline
Reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)=[CH:6][CH:7]=1.[F:14][C:15]([F:30])([C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2)[C:16]([NH:18][NH2:19])=O.CS(O)(=O)=O>COCC(O)C>[F:30][C:15]([F:14])([C:16]1[N:3]2[N:4]=[C:5]([C:8]3[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=3)[CH:6]=[CH:7][C:2]2=[N:19][N:18]=1)[C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][CH:24]=[CH:23]2Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
To a reactor under inert atmosphere was added 73.84 g (0.38 mol) 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine, 90 g (0.38 mol) 2,2-difluoro-2-quinolin-6-ylacetohydrazide and 1200 mL 1-methoxy-2-propanol. Then 29.85 mL (0.455 mol) methane sulphonic acid was added and the reaction mixture was heated at 80° C. for 8 hours. After cooling to ambient temperature the mesylate salt of the title compound was filtered off from the reaction mixture. This salt was dissolved in a mixture of 400 mL ethanol and 300 mL water, after alkalisation at 80° C. with 50 mL ammonia (0.65 mol) in 200 mL water the free base of the title compound precipitates and was filtered off. This precipitate was dried at 50° C. and was subsequently re-crystallized from 2-propanol (1.8 L/mol) to yield the title compound in 75% yield.
Sources & evidence
- ORD record
- ord-fab948e106634ced905aff24968ac977
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08629144B2
Reaction notes
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