Potassium Carbonate → HCID 57505688, compound

HRID 2391452Notes

Reaction equation

HRID 2391452 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[N:13]([CH:15]=[C:16]([NH:18][C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[N:17]=3)[N:14]=2)[CH:5]=[N:6][CH:7]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29]([NH2:31])=[O:30].N[C@@H]1CCCC[C@H]1N.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O1CCCC1.C(OCC)(=O)C.[Cu]I>[CH:21]1([C:19]([NH:18][C:16]2[N:17]=[C:12]3[CH:11]=[CH:10][C:9]([O:8][C:4]4[CH:3]=[C:2]([NH:31][C:29](=[O:30])[C:28]5[CH:32]=[CH:33][CH:34]=[C:26]([C:25]([F:35])([F:36])[F:24])[CH:27]=5)[CH:7]=[N:6][CH:5]=4)=[N:14][N:13]3[CH:15]=2)=[O:20])[CH2:23][CH2:22]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 74535m-(Trifluoromethyl)benzamideHCID 57505687N-[6-[(5-Bromo-3-pyridinyl)oxy]imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505688HCID 57505688, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of N-{6-[(5-bromopyridin-3-yl)oxy]imidazo[1,2-b]pyridazin-2-yl}cyclopropanecarboxamide (200 mg, 0.53 mmol), 3-(trifluoromethyl)benzamide (160 mg, 0.91 mmol), trans-1,2-diaminocyclohexane (15 mg, 0.13 mmol) and potassium carbonate (220 mg, 1.6 mmol) in 1,4-dioxane (3.0 mL) was added copper (I) iodide (25 mg, 0.13 mmol) under argon atmosphere, and the mixture was stirred at 110° C. for 60 hr. The reaction mixture was cooled, and diluted with 20% tetrahydrofuran/ethyl acetate. The mixture was washed with water, 5% aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=60/40→100/0) and precipitated from ethyl acetate/hexane to give the title compound (110 mg, 42%) as a white powder.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe mixture was washed with water, 5% aqueous sodium hydrogencarbonate solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltrated
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=60/40→100/0)
  7. customprecipitated from ethyl acetate/hexane

Sources & evidence

ORD record
ord-c3e273708aa7452f86b8ea9fac212335
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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