Trifluoroiodomethane → 3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-7-trifluoromethyl-1,2,4-triazolo[4,3-b]pyridazine

HRID 2306605Notes

Reaction equation

HRID 2306605 reaction equation
I[C:2]([F:5])([F:4])[F:3].Br[C:7]1[C:12]([O:13][CH2:14][C:15]2[N:16]([CH3:20])[N:17]=[CH:18][N:19]=2)=[N:11][N:10]2[C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])=[N:22][N:23]=[C:9]2[CH:8]=1>CN(C=O)C.ClCCl.[Cu]>[F:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:21]1[N:10]2[N:11]=[C:12]([O:13][CH2:14][C:15]3[N:16]([CH3:20])[N:17]=[CH:18][N:19]=3)[C:7]([C:2]([F:5])([F:4])[F:3])=[CH:8][C:9]2=[N:23][N:22]=1

Participants

6

Reactant 2

HCID 16843TrifluoroiodomethaneHCID 154861777-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 226099083-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-7-trifluoromethyl-1,2,4-triazolo[4,3-b]pyridazineYield 6.2%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Iodotrifluoromethane (2.0 g, 10 mmol) was bubbled through a solution of 7-bromo-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.10 g, 0.25 mmol) in dry DMF (2 ml) at room temperature until the required quantity of gas had dissolved. Copper powder (0.16 g, 2.5 mmol) was added and the mixture was stirred in a sealed tube at 80° C. for 18 h. The mixture was cooled, diluted with dichloromethane (50 ml) and filtered. The filtrate was washed with water (50 ml), then dried (Na2SO4), filtered and concentrated. Preparative thin layer chromatography, eluting with 3% methanol-dichloromethane, gave 3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-7-trifluoromethyl-1,2,4-triazolo[4,3-b]pyridazine (0.0061 g, 6%) as a pale yellow solid; m.p. 123-126° C.; 1H NMR (360 MHz, CDCl3) δ 3.92 (3H, s), 5.60 (2H, s), 7.31 (1H, dd, J=8 and 8 Hz), 7.40 (1H, dd, J=8 and 8 Hz), 7.56-7.64 (1H, m), 7.86-7.94 (2H, m), 8.50 (1H, s); MS (ES+) m/e 393 [MH]+.

Workup

  1. dissolutionhad dissolved
  2. temperatureThe mixture was cooled
  3. filtrationfiltered
  4. washThe filtrate was washed with water (50 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washPreparative thin layer chromatography, eluting with 3% methanol-dichloromethane

Sources & evidence

ORD record
ord-f9e900de25bb48de8949d5c752c0f95a
Source dataset
uspto-grants-2004_12
Patent number
US06828322B2

Reaction notes

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