Potassium Carbonate → 2-[2-[1-(2-Methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yl]-propan-2-ol

HRID 451411Notes

Reaction equation

HRID 451411 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[K+].[K+].Cl.Cl.[CH3:34][C:35]1[N:40]=[C:39]([N:41]2[CH2:46][CH2:45][CH:44]([NH2:47])[CH2:43][CH2:42]2)[CH:38]=[CH:37][N:36]=1.Cl[C:49]1[N:54]=[C:53]([C:55]([OH:58])([CH3:57])[CH3:56])[CH:52]=[C:51]([C:59]2[CH:64]=[CH:63][C:62]([C:65]([F:68])([F:67])[F:66])=[CH:61][CH:60]=2)[N:50]=1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:34][C:35]1[N:40]=[C:39]([N:41]2[CH2:46][CH2:45][CH:44]([NH:47][C:49]3[N:54]=[C:53]([C:55]([OH:58])([CH3:57])[CH3:56])[CH:52]=[C:51]([C:59]4[CH:64]=[CH:63][C:62]([C:65]([F:68])([F:66])[F:67])=[CH:61][CH:60]=4)[N:50]=3)[CH2:43][CH2:42]2)[CH:38]=[CH:37][N:36]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 673429791-(2-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochlorideHCID 866336402-[2-Chloro-6-(4-trifluoromethyl-phenyl)pyrimidine-4-yl]-propan-2-ol

Product 1

HCID 533533372-[2-[1-(2-Methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yl]-propan-2-ol

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
20 °C

Procedure

A mixture of palladium (II) acetate (2.7 mg, 0.012 mmol) and 2-(dicyclohexylphosphino)-biphenyl (8.4 mg, 0.024 mmol) in dioxane (1 mL) was stirred under argon at 20° C. for 10 minutes. The resulting catalyst solution was added to a suspension of potassium carbonate (692 mg, 5.0 mmol), 1-(2-methyl-pyrimidin-4-yl)-piperidin-4-ylamine dihydrochloride (80 mg, 0.3 mmol), and 2-[2-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yl]-propan-2-ol (95 mg, 0.3 mmol) in dioxane (1.7 mL). The reaction mixture was heated to 170° C. in a microwave oven for 30 minutes. The reaction mixture was cooled, diluted with water and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using CH2Cl2/0-10% MeOH as eluent. The title compound was obtained as a light yellow solid (9 mg, 6%).

Workup

  1. temperatureThe reaction mixture was heated to 170° C. in a microwave oven for 30 minutes
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted twice with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-ec3add3e1231417a9d04a52a551b5d7c
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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