Sodium Carbonate → 4-(difluoromethyl)-N-(3-methyl-5-(1-(3-methylbut-3-en-2-yl)-1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine

HRID 595306Notes

Reaction equation

HRID 595306 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]([CH:33]([C:35]([CH3:37])=[CH2:36])[CH3:34])[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]([CH:33]([C:35]([CH3:37])=[CH2:36])[CH3:34])[CH:32]=3)[CH:13]=[C:12]([CH3:25])[CH:11]=2)[N:4]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 584561714-(difluoromethyl)-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amineHCID 1182085614-bromo-1-(3-methylbut-3-en-2-yl)-1H-pyrazole

Product 1

HCID 1182088554-(difluoromethyl)-N-(3-methyl-5-(1-(3-methylbut-3-en-2-yl)-1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine

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 4-bromo-1-(3-methylbut-3-en-2-yl)-1H-pyrazole (238 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, 1.1 ml, 2.2 mmol) were added and the reaction was sealed and heated to 90° C. for 12 hours. The reaction was cooled, diluted with water (10 mL), and the product was 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 two times utilizing (10-50% ethyl acetate/hexanes) and (0-5% acetone/dichloromethane) to afford 4-(difluoromethyl)-N-(3-methyl-5-(1-(3-methylbut-3-en-2-yl)-1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine. MS ESI calcd. for C20H22F2N5 [M+H]+ 370. found 370.

Workup

  1. customdegassed with nitrogen for 5 minutes
  2. customthe reaction was sealed
  3. temperatureThe reaction was cooled
  4. extractionthe product was extracted 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 two times utilizing (10-50% ethyl acetate/hexanes) and (0-5% acetone/dichloromethane)

Sources & evidence

ORD record
ord-2d08057f013144f89d16b6675a7cbac0
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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