Cesium carbonate → HCID 86682404, compound

HRID 2365255Notes

Reaction equation

HRID 2365255 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11]3[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=3[C:13]3[CH2:14][NH:15][C:16](=[O:19])[C:17]=3[CH:18]=2)=[CH:5][CH:4]=1.Br[C:25]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[CH:27][N:26]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11]3[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=3[C:13]3[CH2:14][N:15]([C:25]4[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[CH:27][N:26]=4)[C:16](=[O:19])[C:17]=3[CH:18]=2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 51938202-bromo-3-trifluoromethylpyridineHCID 56643780HCID 56643780, compound

Product 1

HCID 86682404HCID 86682404, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-[(6-methoxypyridin-3-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one (0.050 g, 0.16 mmol) in 1 mL of dioxane under an atmosphere of nitrogen was added 2-bromo-3-(trifluoromethyl)pyridine (0.037 g, 0.16 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.014 g, 0.025 mmol), cesium carbonate (0.075 g, 0.23 mmol), and tris[dibenzylideneacetone]dipalladium (0) (7.5 mg, 0.0082 mmol). The mixture was irradiated in a microwave reactor at 140° C. for 1.5 hr, cooled to ambient temperature, and diluted with ethyl acetate. The organic solution was washed with water, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 450.1423 for [M+H]+ [calc'd for C25H19F3N3O2, [M+H]+=450.1424]: 1H NMR (400 MHz, CDCl3) δ 8.79-8.77 (m, 1H), 8.20-8.12 (m, 3H), 7.95-7.91 (m, 1H), 7.76 (s, 1H), 7.69-7.62 (m, 2H), 7.52-7.44 (m, 2H), 6.71 (d, J=8.6 Hz, 1H), 5.34 (s, 2H), 4.46 (s, 2H), 3.94 (s, 3H) ppm.

Workup

  1. customThe mixture was irradiated in a microwave reactor at 140° C. for 1.5 hr
  2. washThe organic solution was washed with water
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-dab2656bd0c3434e9c6e1eb822c6855c
Source dataset
uspto-grants-2014_04
Patent number
US08697690B2

Reaction notes

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