Triethylamine → 3-(Imidazo[1,2-b]pyridazin-6-ylethynyl)aniline

HRID 589912Notes

Reaction equation

HRID 589912 reaction equation
O[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.C(N(CC)CC)C.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:58]([C:60]1[CH:61]=[C:62]([CH:64]=[CH:65][CH:66]=1)[NH2:63])#[CH:59]>CN(C=O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[N:10]1[CH:9]=[CH:8][N:6]2[C:5]=1[CH:4]=[CH:3][C:2]([C:59]#[C:58][C:60]1[CH:61]=[C:62]([CH:64]=[CH:65][CH:66]=1)[NH2:63])=[N:7]2

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 104682Benzenamine, 3-ethynyl-HCID 142176Phenyl triflimideHCID 178515753HCID 178515753, compound

Product 1

HCID 1186384153-(Imidazo[1,2-b]pyridazin-6-ylethynyl)aniline

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring mixture of 6-hydroxyimidazo[1,2-b]pyridazine (2.06 g, 15.259 mmol, 1 eq) in anhydrous DMF (20 mL) under nitrogen atmosphere was added triethylamine (8.51 mL, 4 eq) and N-phenyl-bis(trifluoromethanesulfonimide) (5.386 g, 1 eq). After the reaction was stirred at room temperature for 18 hours, to the reaction was added triphenylphosphine (100 mg, 0.025 eq), bis(triphenylphosphine)palladium(II) dichloride (1.07 g, 0.1 eq), copper(I) iodide (581 mg, 0.2 eq), and 3-ethynylaniline (2.394 mL, 1.5 eq) under nitrogen atmosphere. The resulting reaction mixture was heated at 60° C. for two hours. The reaction was then cooled to room temperature, diluted with ethyl acetate, washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine, and lastly dried with anhydrous sodium sulfate. The upper solution was decanted, concentrated, the residue mixture was subject to a gradient column chromatography (from DCM to MeOH-DCM 1:25). The product fractions were collected, concentrated, and the residue was triturated with EtOAc-Hex (˜1:5) to give 3-(imidazo[1,2-b]pyridazin-6-ylethynyl)aniline as a fluffy slightly yellow solid upon filtration in amount of 2.384 g (67%).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated at 60° C. for two hours
  3. temperatureThe reaction was then cooled to room temperature
  4. washwashed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine
  5. dry with materiallastly dried with anhydrous sodium sulfate
  6. customThe upper solution was decanted
  7. concentrationconcentrated
  8. customThe product fractions were collected
  9. concentrationconcentrated
  10. customthe residue was triturated with EtOAc-Hex (˜1:5)

Sources & evidence

ORD record
ord-56c80f63f9c34e66ba65b4845b762e31
Source dataset
uspto-grants-2016_01
Patent number
US09233968B1

Reaction notes

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