HCID 86692118, compound → HCID 86692117, compound

HRID 876869Notes

Reaction equation

HRID 876869 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].[Cl-].[CH3:36][Zn+]>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]([CH3:36])=[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

4

Reactant 2

HCID 86692118HCID 86692118, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 86692117HCID 86692117, compoundYield 21.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

101 mg (0.19 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 0.95 mL THF. After addition of 0.49 mL (0.97 mmol) of methylzinc chloride (2M solution in THF) and 7.9 mg (0.01 mmol) bis(diphenylphosphino)ferrocenedichloropalladium(II) the reaction mixture was heated for 40′ in the microwave at 100° C. The reaction mixture was poured on water (30 mL) and extracted twice with ethyl acetate (50 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 18.5 mg of the desired compound which was 90% pure.

Workup

  1. additionThe reaction mixture was poured on water (30 mL)
  2. extractionextracted twice with ethyl acetate (50 mL each)
  3. washThe combined organic extracts were washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationAfter filtration and evaporation of the solvent the residue
  6. customwas purified by chromatography on silicagel (eluents: dichloromethane/methanol)

Sources & evidence

ORD record
ord-11dfc3c3edf34a99a0267b155e19ef5c
Source dataset
uspto-grants-2015_03
Patent number
US08987273B2

Reaction notes

Loading…