Sodium Carbonate → 1-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)propan-2-one

HRID 595309Notes

Reaction equation

HRID 595309 reaction equation
[F:1][CH:2]([F:26])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:15]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:13]=[C:12]([CH3:25])[CH:11]=2)[N:4]=1.Br[C:28]1[CH:29]=[N:30][N:31]([CH2:33][C:34](=[O:36])[CH3:35])[CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:26][CH:2]([F:1])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:15]=[C:14]([C:28]3[CH:29]=[N:30][N:31]([CH2:33][C:34](=[O:36])[CH3:35])[CH:32]=3)[CH:13]=[C:12]([CH3:25])[CH:11]=2)[N:4]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 195769081-(4-bromo-1H-pyrazol-1-yl)propan-2-oneHCID 584561714-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine

Product 1

HCID 1182087981-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)propan-2-one

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-(Difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (400 mg, 1.11 mmol) and 1-(4-bromo-1H-pyrazol-1-yl)propan-2-one (225 mg, 1.11 mmol) were dissolved in dioxane (4 mL) and degassed with nitrogen for 5 minutes. PdCl2(dppf)-CH2Cl2 (90 mg, 0.11 mmol) and sodium carbonate (2.0 M in water, 1.107 ml, 2.215 mmol) were added, the reaction was sealed and heated to 90° C. for 12 hours. The reaction was cooled to ambient temperature, diluted with water (10 mL) and product extracted with ethyl acetate (2×20 mL). The extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by column chromatography on silica (5-50% ethyl acetate/hexanes) to afford 1-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)propan-2-one. MS ESI calcd. for C18H18F2N5O [M+H]+ 358. found 358.

Workup

  1. customdegassed with nitrogen for 5 minutes
  2. customthe reaction was sealed
  3. temperatureThe reaction was cooled to ambient temperature
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. dry with materialThe extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford the crude product residue
  9. customThe crude product residue was purified by column chromatography on silica (5-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fb67d5e30c164400b63a008bae3995bc
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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