Imidazole → tert-butyl N-[(E)-[2-(2,2-difluoro-2-quinolin-6-ylacetyl)-6-(1-methylpyrazol-4-yl)pyridazin-3-ylidene]amino]carbamate
Reaction equation
[F:1][C:2]([F:16])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][CH:10]=[CH:9]2)[C:3]([O-:5])=O.[Na+].[CH3:18][N:19]1[CH:23]=[C:22]([C:24]2[N:29]=[N:28][C:27]([NH:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:26][CH:25]=2)[CH:21]=[N:20]1.N1C=CN=C1.S(Cl)(Cl)=O>C(#N)C>[F:16][C:2]([F:1])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][CH:10]=[CH:9]2)[C:3]([N:28]1[N:29]=[C:24]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)[CH:25]=[CH:26]/[C:27]/1=[N:30]\[NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[O:5]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
900 mg (3.67 mmol) of sodium difluoro(quinolin-6-yl)acetate was dissolved in acetonitrile (27 mL). 1.17 g (4.04 mmol) of tert-butyl 2-[6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl]hydrazinecarboxylate was added and 300 mg (4.41 mmol) of 1H-imidazole was added at once. 0.561 mL (7.71 mmol) of thionyl chloride was added over 5 minutes at room temperature. The mixture was stirred for 2 hours at room temperature, giving tert-butyl (2E)-2-{2-[difluoro(quinolin-6-yl)acetyl]-6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3(2H)-ylidene}hydrazinecarboxylate. Then, 0.722 mL (11.0 mmol) of methanesulphonic acid was added at room temperature and stirred for 16 h. The resulting solids were filtered off under argon atmosphere, yielding 6-{1,1-difluoro-2-[(6E)-6-hydrazono-3-(1-methyl-1H-pyrazol-4-yl)pyridazin-1(6H)-yl]-2-oxoethyl}quinoline and used as such in the next step.
Sources & evidence
- ORD record
- ord-060c0b37fd864b569deb3003c49ddd74
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08629144B2
Reaction notes
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