Triethylamine → N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

HRID 589911

Reaction equation

HRID 589911 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH2:11])[N:10]=2)[N:7]=1.C(N(CC)CC)C.[C:19]([C:21]1[CH:22]=[C:23]([NH:27][C:28](=[O:37])[C:29]2[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=2[F:36])[CH:24]=[CH:25][CH:26]=1)#[CH:20]>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>[NH2:11][C:9]1[N:10]=[C:5]2[CH:4]=[CH:3][C:2]([C:20]#[C:19][C:21]3[CH:22]=[C:23]([NH:27][C:28](=[O:37])[C:29]4[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:30]=4[F:36])[CH:24]=[CH:25][CH:26]=3)=[N:7][N:6]2[CH:8]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 574410246-Iodoimidazo[1,2-B]pyridazin-2-amineHCID 62510676N-(3-ethynylphenyl)-2-fluoro-5-methylbenzamide

Product 1

HCID 118638430N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

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 the nitrogen bubbled solution of 6-iodo-imidazo[1,2-b]pyridazin-2-ylamine (52 mg, 0.2 mmol, 1 eq) in anhydrous DMF (2 mL) was added triethylamine (0.11 mL, 4 eq), bis(triphenylphosphine)palladium(II) dichloride (14 mg, 0.1 eq), copper(I) iodide (7.6 mg, 0.2 eq), and N-(3-ethynylphenyl)-2-fluoro-5-methylbenzamide (76 mg, 1.5 eq). after the mixture was stirred at room temperature for 30 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 [EtOAc-Hex 1:2 to 3:1 (with 1% v/v MeOH added)]. The product fractions were collected, concentrated, the residue was further triturated with ethyl acetate to give N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide as a yellow solid in amount of 23 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. additionadded)]
  6. customThe product fractions were collected
  7. concentrationconcentrated
  8. customthe residue was further triturated with ethyl acetate

Sources & evidence

ORD record
ord-8499f186f1824029b761d9b7de5f6208
Source dataset
uspto-grants-2016_01
Patent number
US09233968B1

Linked notes

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