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

HRID 589905Notes

Reaction equation

HRID 589905 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[C:17]([C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[CH:30]=2)=[O:27])=[CH:21][CH:20]=1)#[CH:18].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>[CH3:35][C:31]1[CH:30]=[C:29]([NH:28][C:26]([NH:25][C:22]2[CH:21]=[CH:20][C:19]([C:17]#[C:18][C:2]3[CH:3]=[CH:4][C:5]4[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]5[CH2:16][CH2:15]5)=[O:13])[N:10]=4)[N:7]=3)=[CH:24][CH:23]=2)=[O:27])[CH:34]=[CH:33][CH:32]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 57386058N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamideHCID 1186384341-(4-Ethynylphenyl)-3-(3-methylphenyl)urea

Product 1

HCID 118638412N-(6-{[4-({[(3-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

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 mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (50 mg, 0.152 mmol, 1 eq) and 1-(4-ethynylphenyl)-3-(3-methylphenyl)urea (57 mg, 1.5 eq) in anhydrous DMF (1 mL) under nitrogen atmosphere was added triethylamine (0.085 mL, 4 eq), bis(triphenylphosphine)palladium(II) dichloride (10.7 mg, 0.1 eq) and copper(I) iodide (5.8 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 solid residue was subject to a gradient column chromatography (from DCM to MeOH-DCM 1:9). The products' fractions were collected, concentrated, and the solid residue was triturated with EtOAc-Hex (6:1) to give N-(6-{[4-({[(3-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide as a brown solid upon filtration in amount of 46 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
  5. customThe products' fractions were collected
  6. concentrationconcentrated
  7. customthe solid residue was triturated with EtOAc-Hex (6:1)

Sources & evidence

ORD record
ord-a0e217dd2edb47f28cfd437a5735224d
Source dataset
uspto-grants-2016_01
Patent number
US09233968B1

Reaction notes

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