Water → N-[3-(6-methoxypyridin-3-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

HRID 2207362Notes

Reaction equation

HRID 2207362 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[CH:13][CH:14]=2)O1.[F-].[K+].Br[C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[N:34][CH:35]=1.O>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:37][O:36][C:33]1[N:34]=[CH:35][C:30]([C:9]2[CH:10]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][N:17]=3)[CH:12]=[CH:13][CH:14]=2)=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 27348955-Bromo-2-methoxypyridineHCID 58456307N-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 131735890N-[3-(6-methoxypyridin-3-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (150 mg, 0.411 mmol) and potassium fluoride (71.6 mg, 1.23 mmol) were added to 3.00 mL of a stock solution of palladium(II) acetate (4.61 mg, 0.021 mmol) and butyl[di-(3S,5S,7S)-tricyclo[3.3.1.13,7]dec-1-yl]phosphane (14.7 mg, 0.041 mmol) in THF (3.00 mL) under nitrogen. 5-Bromo-2-methoxypyridine (0.069 mL, 0.534 mmol) and water (1.00 mL) were then added to the reaction mixture and was heated to 75° C. for 17 hours. Upon cooling to room temperature, the reaction mixture was quenched by the addition of 25% aqueous NH4OAc. The aqueous layer was extracted with ethyl acetate (2×) and the combined organic layers were washed sequentially with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/dichloromethane) to afford N-[3-(6-methoxypyridin-3-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine as a beige solid. MS APC calc'd for C17H14F3N4O [M+H]+ 347. found 347.

Workup

  1. temperatureUpon cooling to room temperature
  2. customthe reaction mixture was quenched by the addition of 25% aqueous NH4OAc
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  4. washthe combined organic layers were washed sequentially with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-3eeba411ec794bee9875222cf48edde3
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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