Methanol → HCID 58003465, compound

HRID 1667882Notes

Reaction equation

HRID 1667882 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]3[N:11]([CH:13]=[C:14]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])[N:15]=3)[N:12]=2)=[CH:4][C:3]=1[N+:24]([O-])=O.CO.[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][C:34]([N:37]=[C:38]=S)=[CH:33][CH:32]=1>[C].[Pd].[Fe](Cl)(Cl)Cl.C(OCC)(=O)C>[F:29][C:30]([F:40])([F:41])[C:31]1[CH:32]=[CH:33][C:34]([NH:37][C:38]2[NH:24][C:3]3[CH:4]=[C:5]([O:6][C:7]4[CH:8]=[CH:9][C:10]5[N:11]([CH:13]=[C:14]([NH:16][C:17]([CH:19]6[CH2:21][CH2:20]6)=[O:18])[N:15]=5)[N:12]=4)[CH:22]=[CH:23][C:2]=3[N:1]=2)=[CH:35][CH:36]=1

Participants

7

Reactant 3

HCID 887MethanolHCID 1371344-(Trifluoromethyl)phenyl isothiocyanateHCID 57505458HCID 57505458, compound

Product 1

HCID 58003465HCID 58003465, compoundYield 126.1%

Reagents, catalysts & solvents 3

HCID 24380Iron chloride (FeCl3)CatalystHCID 178418390HCID 178418390, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of N-[6-(4-amino-3-nitrophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (499 mg, 1.38 mmol), 10% palladium carbon (100 mg) and methanol (20.0 mL) was stirred under a hydrogen atmosphere (up to 1 atm) at room temperature overnight. The insoluble material was filtered through celite, and the filtrate was evaporated under reduced pressure. The residue was dissolved in methanol (10 mL), 4-(trifluoromethyl)phenylisothiocyanate (120 mg, 0.59 mmol) was added to the mixture, and the mixture was stirred at room temperature for 1 hr. Iron (III) chloride (177 mg, 1.1 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for 1.5 hr. Ethyl acetate was added to the reaction mixture, and the mixture was washed with saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and filtrated. Dichloromethane (20 mL) was added to the residue, and the precipitate was collected by filtration to give the title compound (367 mg, 52%). The filtrate was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate alone→ethyl acetate/methanol=9:1). Ethyl acetate was added to the obtained oily substance, and the precipitate was collected by filtration to give the title compound (116 mg, 32%) as a pale-yellow solid.

Workup

  1. filtrationThe insoluble material was filtered through celite
  2. customthe filtrate was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in methanol (10 mL)
  4. stirringthe mixture was stirred at room temperature for 1 hr
  5. stirringthe mixture was further stirred at room temperature for 1.5 hr
  6. washthe mixture was washed with saturated aqueous sodium hydrogencarbonate solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltrated
  9. additionDichloromethane (20 mL) was added to the residue
  10. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-b638da52c3ff40669c3ff251c6014635
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

Loading…