HCID 86692118, compound → HCID 86692119, compound

HRID 876870Notes

Reaction equation

HRID 876870 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:20][C:21]4[N:22]([C:24](Br)=[CH:25][N:26]=4)[N:23]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:20][C:21]4[N:22]([C:24]([C:14]5[CH:15]=[CH:16][CH:17]=[C:12]([C:8]#[N:7])[CH:13]=5)=[CH:25][N:26]=4)[N:23]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 86692118HCID 86692118, compound

Product 1

HCID 86692119HCID 86692119, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

311 mg (0.6 mmol) {1-[4-(3-Bromo-7-phenyl-imidazo[1,2-b]pyridazin-6-yl)-phenyl]-cyclobutyl}-carbamic acid tert.-butyl ester, intermediate example Int-2-1, were dissolved in 6.2 mL THF. After addition of 6 mL (3 mmol) of 3-(cyanophenyl)zinc iodide (0.5M solution in THF) and 23 mg (0.03 mmol) bis(diphenylphosphino)ferrocenedichloropalladium(II) the reaction mixture was heated for 40′ in the microwave at 100° C. Additional 6 mL (3 mmol) of 3-(cyanophenyl)zinc iodide (0.5M solution in THF) and 46 mg (0.06 mmol) catalysator were added and the mixture was heated in the microwave for an additional hour at 100° C. The reaction mixture was poured on water (100 mL) and extracted twice with ethyl acetate (100 mL each). The combined organic extracts were washed with water and dried over sodium sulfate. After filtration and evaporation of the solvent the residue was purified by chromatography on silicagel (eluents: dichloromethane/methanol) yielding 121 mg of the desired compound which however were strongly contaminated.

Workup

  1. temperaturethe mixture was heated in the microwave for an additional hour at 100° C
  2. additionThe reaction mixture was poured on water (100 mL)
  3. extractionextracted twice with ethyl acetate (100 mL each)
  4. washThe combined organic extracts were washed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration and evaporation of the solvent the residue
  7. customwas purified by chromatography on silicagel (eluents: dichloromethane/methanol)

Sources & evidence

ORD record
ord-6d9dea09a03448dbb956bf28836b2d63
Source dataset
uspto-grants-2015_03
Patent number
US08987273B2

Reaction notes

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