Potassium Phosphate, Tribasic → HCID 68322460, compound

HRID 1505391Notes

Reaction equation

HRID 1505391 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([NH2:15])=[CH:11][N:10]=2)=[CH:4][C:3]=1[O:16][C:17]([F:20])([F:19])[F:18].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:29]B(O)O>CN(C=O)C.O>[CH3:29][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([NH2:15])=[CH:11][N:10]=2)=[CH:4][C:3]=1[O:16][C:17]([F:20])([F:19])[F:18]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic AcidHCID 67236644HCID 67236644, compound2×

Product 1

HCID 68322460HCID 68322460, compoundYield 61.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-({4-bromo-3-[(trifluoromethyl)oxy]phenyl}oxy)-5-pyrimidinamine (Intermediate 162, 270 mg) in DMF (4 mL) were added K3PO4 (490 mg, 2.31 mmol), Pd(tBu3)2 (197 mg, 0.385 mmol) and methyl boronic acid (276 mg, 4.62 mmol) and the reaction mixture was stirred for 30 minutes at 110° C. under microwave irradiation. After cooling the reaction was diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). The organic layer was washed with ice cold brine (2×5 mL), dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography on silica gel (SNAP 10 g) eluting from 80:20 to 50:50 cyclohexane/ethyl acetate to afford the title compound as white solid (135 mg).

Workup

  1. temperatureAfter cooling the reaction
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe organic layer was washed with ice cold brine (2×5 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customthe residue was purified by flash chromatography on silica gel (SNAP 10 g)
  8. washeluting from 80:20 to 50:50 cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-f3dfc4d5c8c6481c892d265f637b37c8
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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