Cesium carbonate → 4-(1-fluoroethyl)-N-(3-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine

HRID 595311Notes

Reaction equation

HRID 595311 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]([F:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:59][C:60]1[CH:61]=[C:62]([CH:64]=[C:65]([C:67]2[CH:68]=[N:69][N:70]([CH2:72][C:73]([CH3:75])=[CH2:74])[CH:71]=2)[CH:66]=1)[NH2:63]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:10][CH:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:63][C:62]2[CH:64]=[C:65]([C:67]3[CH:68]=[N:69][N:70]([CH2:72][C:73]([CH3:75])=[CH2:74])[CH:71]=3)[CH:66]=[C:60]([CH3:59])[CH:61]=2)[N:7]=1)[CH3:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866582372-Chloro-4-(1-fluoroethyl)pyrimidineHCID 1182086423-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)aniline

Product 1

HCID 1182086224-(1-fluoroethyl)-N-(3-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

2-Chloro-4-(1-fluoroethyl)pyrimidine (170 mg, 1.06 mmol), Palladium(II) acetate (59.3 mg, 0.26 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (229 mg, 0.40 mmol), and cesium carbonate (860 mg, 2.64 mmol) were added to a solution of 3-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)aniline (300 mg, 1.32 mmol) in dioxane (2.5 mL). The solution was degassed by sparging with Ar for 5 minutes and stirred at 110° C. for 18 h. The mixture was allowed to cool to room temperature, diluted with EtOAc, and washed with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (10-30% EtOAc/Hexane), then further purified by reverse phase HPLC (ACN/water with 0.1% TFA modifier) to afford 4-(1-fluoroethyl)-N-(3-methyl-5-(1-(2-methylallyl)-1H-pyrazol-4-yl)phenyl)pyrimidin-2-amine MS ESI calc'd. for C20H23FN5 [M+H]+ 352. found 352.

Workup

  1. customThe solution was degassed
  2. customby sparging with Ar for 5 minutes
  3. temperatureto cool to room temperature
  4. additiondiluted with EtOAc
  5. washwashed with brine
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel (10-30% EtOAc/Hexane)
  10. customfurther purified by reverse phase HPLC (ACN/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-5a65205af67d4972abb1685dc6e1b1c4
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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