Potassium Phosphate, Tribasic → tert-butyl 4-[4-(2-aminopyrimidin-5-yl)-2-fluorophenyl]-1H-pyrazol-1-ylacetate

HRID 500199Notes

Reaction equation

HRID 500199 reaction equation
[C:1]([O:5][C:6](=[O:21])[CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][C:14]=2[F:20])[CH:10]=[N:9]1)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:16]2[CH:17]=[CH:18][C:13]([C:11]3[CH:10]=[N:9][N:8]([CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:21])[CH:12]=3)=[C:14]([F:20])[CH:15]=2)=[CH:31][N:32]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 86654279tert-butyl[4-(4-bromo-2-fluorophenyl)-1H-pyrazol-1-yl]acetate

Product 1

HCID 67223819tert-butyl 4-[4-(2-aminopyrimidin-5-yl)-2-fluorophenyl]-1H-pyrazol-1-ylacetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl[4-(4-bromo-2-fluorophenyl)-1H-pyrazol-1-yl]acetate (400 mg, 0.001 mol) in 1,4-dioxane (3 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (270 mg, 1.2 mmol), potassium phosphate (640 mg, 3.0 mmol) and tetrakis(triphenylphosphine)palladium (70 mg, 0.06 mmol). The solution was degassed with N2, and heated at 120° C. for 3 h. The solution was cooled to RT, poured into water, extracted with EtOAc, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatograph on a silica gel column with EtOAc in Hexanes (50%) to afford the desired compound. LCMS: (M+H)=370.1.

Workup

  1. customThe solution was degassed with N2
  2. temperatureThe solution was cooled to RT
  3. additionpoured into water
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatograph on a silica gel column with EtOAc in Hexanes (50%)

Sources & evidence

ORD record
ord-269d096147cb414fb1c9d87f0987747f
Source dataset
uspto-grants-2010_08
Patent number
US07767675B2

Reaction notes

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