Triethylamine → 6-chloro-3-(2-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazine
Reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][NH2:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:17][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](O)=O>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:20]([C:19]3[CH:23]=[CH:24][CH:25]=[CH:26][C:18]=3[F:17])=[N:9][N:8]=2)[N:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
6-Chloro-3-hydrazinopyridazine (6.9 mmol) was suspended in dioxane (45 mL) with triethylamine (1.1 equiv), and the acyl chloride of 2-fluorobenzoic acid (1.1 equiv) in dioxane (10 ml) was added dropwise over 5-10 min at room temperature. The reaction mixture was stirred at the same temperature for 30-50 min (monitored by TLC), and then the dioxane was removed by rotary evaporation. The residue was refluxed in phosphorus oxychloride (40 ml) for 3-4 hours, and then the solvent was evaporated. 6-Chloro-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine was obtained by washing the residue several times with ethyl acetate followed by filtration then adding ice-cold water (50 ml) to the residue. The aqueous layer was neutralized to pH 7 with saturated aqueous sodium hydrogen carbonate, and the resulting solid was collected by filtration, washed twice with water and then with hexane, and dried under vacuum at 50° C. 1H NMR (400 MHz, Me2SO-d6): 8.57 (d, 1H, pyridazine, J=9.3 Hz), 7.85-7.89 (td, 1H, Ph, J=1.6 Hz and 7.4 Hz), 7.68-7.72 (m, 1H, Ph), 7.58 (d, 1H, pyridazine, J=9.4 Hz), 7.45-7.53 (m, 2H, Ph). FABMS (M+H) calculated for C11H6ClFN4.H was 249.0337. found 249.0339.
Workup
- customthe dioxane was removed by rotary evaporation
- temperatureThe residue was refluxed in phosphorus oxychloride (40 ml) for 3-4 hours
- customthe solvent was evaporated
Sources & evidence
- ORD record
- ord-84ef94f8db4a4d409b667db27ae349b8
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09187484B2
Reaction notes
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