Hydrochloric Acid → 3-oxa-8-azabicyclo[3.2.1]oct-8-yl(8-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone

HRID 931034Notes

Reaction equation

HRID 931034 reaction equation
[CH:1]12[N:8]([C:9]([C:11]3[N:15]4[CH:16]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:19](Br)[C:14]4=[N:13][CH:12]=3)=[O:10])[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][CH2:2]2.[NH:25]1[CH:29]=[N:28][CH:27]=[N:26]1.N1C2C(=CC=CC=2O)C=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.[Cu]I>[CH:1]12[N:8]([C:9]([C:11]3[N:15]4[CH:16]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:19]([N:25]5[CH:29]=[N:28][CH:27]=[N:26]5)[C:14]4=[N:13][CH:12]=3)=[O:10])[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][CH2:2]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 19238-HydroxyquinolineHCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 1183789383-Oxa-8-azabicyclo[3.2.1]octan-8-yl(8-bromo-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone

Product 1

HCID 1183789583-oxa-8-azabicyclo[3.2.1]oct-8-yl(8-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanoneYield 7.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
170 °C

Procedure

A mixture of 3-oxa-8-azabicyclo[3.2.1]octan-8-yl(8-bromo-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)methanone (315 mg), 1H-1,2,4-triazole (108 mg), copper(I) iodide (44.5 mg), 8-quinolinol (33.9 mg) and potassium carbonate (215 mg) in DMSO (3.0 mL) was stirred with microwave irradiation at 170° C. for 30 min. To the reaction mixture was added 0.1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous ammonium chloride solution and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (22.0 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated aqueous ammonium chloride solution and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  6. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-65b53583b6cb49fd8931ab03e9bee36a
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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