Sodium Carbonate → N-(4-(2'-fluoro-5-methoxy-3,4'-bipyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine

HRID 473745Notes

Reaction equation

HRID 473745 reaction equation
Br[C:2]1[C:3]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[CH:13][CH:12]=2)=[N:4][CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[F:25][C:26]1[CH:31]=[C:30](B(O)O)[CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:26]1[CH:31]=[C:30]([C:2]2[C:3]([O:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=4)=[CH:13][CH:12]=3)=[N:4][CH:5]=[C:6]([O:8][CH3:9])[CH:7]=2)[CH:29]=[CH:28][N:27]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 59374202N-(4-(3-bromo-5-methoxypyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine

Product 1

HCID 46834094N-(4-(2'-fluoro-5-methoxy-3,4'-bipyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

N-(4-(3-bromo-5-methoxypyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine (0.076 g, 0.20 mmol), 2-fluoropyridine-4-boronic acid (0.056 g, 0.39 mmol), and tetrakis(triphenylphosphine)palladium (0.023 g, 0.020 mmol) were mixed in dioxane (0.8 mL) under an argon atmosphere. Sodium carbonate (0.30 mL, 0.59 mmol, 2.0 M in water) was added via syringe, and the reaction mixture was stirred at 80° C. for 20 h before being warmed to 90° C. and stirred for 24 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc. The organic layer was separated, washed with sat. sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel chromatography to give N-(4-(2′-fluoro-5-methoxy-3,4′-bipyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine. MS (ESI, pos. ion) m/z: 403.2 (M+1). IC50 (uM) 0.004.

Workup

  1. temperaturebefore being warmed to 90° C.
  2. stirringstirred for 24 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with EtOAc
  5. customThe organic layer was separated
  6. washwashed with sat. sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e1c73e18fae74450940756a4a8624851
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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