Triethylamine → N-(6-{[4-({[(3-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 589903Notes

Reaction equation

HRID 589903 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=2)[N:7]=1.[C:15]([C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[CH:28]=2)=[O:25])=[CH:19][CH:18]=1)#[CH:16].C(N(CC)CC)C>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>[CH3:33][C:29]1[CH:28]=[C:27]([NH:26][C:24]([NH:23][C:20]2[CH:19]=[CH:18][C:17]([C:15]#[C:16][C:2]3[CH:3]=[CH:4][C:5]4[N:6]([CH:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[N:10]=4)[N:7]=3)=[CH:22][CH:21]=2)=[O:25])[CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 57441059N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)acetamideHCID 1186384341-(4-Ethynylphenyl)-3-(3-methylphenyl)urea

Product 1

HCID 118638436N-(6-{[4-({[(3-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}imidazo[1,2-b]pyridazin-2-yl)acetamide

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 solution of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide (65 mg, 0.215 mmol, 1 eq) and 1-(4-ethynylphenyl)-3-(3-methylphenyl)urea (80.7 mg, 1.5 eq) in anhydrous DMF (2 mL) under nitrogen atmosphere was added triethylamine (0.12 mL, 4 eq), bis(triphenylphosphine)palladium(II) dichloride (15 mg, 0.1 eq) and copper(I) iodide (8.2 mg, 0.2 eq). After the reaction mixture was stirred at room temperature for 10 minutes, it was 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, and the oily residue was wrapped with silica gel which was subject to a gradient column chromatography (from DCM to MeOH-DCM 1:9) to give N-(6-{[4-({[(3-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}imidazo[1,2-b]pyridazin-2-yl)acetamide as a brown solid in amount of 31 mg.

Workup

  1. washwashed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine
  2. dry with materiallastly dried with anhydrous sodium sulfate
  3. customThe upper solution was decanted
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7345e1da24d1472fa460e3d5a4732ea1
Source dataset
uspto-grants-2016_01
Patent number
US09233968B1

Reaction notes

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