Cesium fluoride → HCID 59187371, compound

HRID 1802356Notes

Reaction equation

HRID 1802356 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]([F:15])=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=2)=[CH:4][C:3]=1[C:16]([O:18][CH3:19])=[O:17].C([Sn](CCCC)(CCCC)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)CCC.[F-].[Cs+]>CN(C)C=O.C(OCC)(=O)C.[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:15][C:9]1[C:8]([C:5]2[CH:4]=[C:3]([C:16]([O:18][CH3:19])=[O:17])[C:2]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)=[N:7][CH:6]=2)=[CH:13][C:12]([CH3:14])=[CH:11][N:10]=1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 6077842-(Tributylstannyl)pyridineHCID 59187386HCID 59187386, compound

Product 1

HCID 59187371HCID 59187371, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

To a solution of methyl 6-chloro-2′-fluoro-5′-methyl-3,3′-bipyridine-5-carboxylate (11-2, 0.098 g, 0.35 mmol, 1.0 equiv) in dimethylformamide (2.3 mL) was added 2-tri-n-butylstannylpyridine (0.26 g, 0.70 mmol, 2.0 equiv), cesium fluoride (0.16 g, 1.05 mmol, 3.0 equiv), copper (I) iodide (0.013 g, 0.070 mmol, 0.2 equiv), and tetrakis(triphenylphosphine)-palladium(0) (0.040 g, 0.035 mmol, 0.1 equiv) and the system was heated to 135° C. for 10 minutes in a microwave reactor. The reaction mixture was cooled and diluted with ethyl acetate (30 mL) and the reaction mixture was filtered through a pad of celite. The reaction mixture was washed with water (3×10 mL) and brine (1×10 mL), dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (10 to 100% EtOAc in hexanes, silica) to afford the desired product (11-3) as an oily solid after concentration. ESI+MS [M+H]+ C18H14FN3O2 calc'd 324.1. found 324.0.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationthe reaction mixture was filtered through a pad of celite
  3. washThe reaction mixture was washed with water (3×10 mL) and brine (1×10 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified via normal phase chromatography (10 to 100% EtOAc in hexanes, silica)

Sources & evidence

ORD record
ord-0999d83203ce4205bfd96e1d14cf09a6
Source dataset
uspto-grants-2013_01
Patent number
US08349872B2

Reaction notes

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