Cesium carbonate → 5-Isopropenyl-2-[4-[2-(4-methanesulfonylphenoxymethyl)pyridin-5-yl]piperidin-1-yl]pyrimidine

HRID 42164

Reaction equation

HRID 42164 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[CH:15]=[CH:16][C:17]([CH2:20][O:21][C:22]4[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=4)=[N:18][CH:19]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[C:32](B1OC(C)(C)C(C)(C)O1)([CH3:34])=[CH2:33].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O>[C:32]([C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[CH:15]=[CH:16][C:17]([CH2:20][O:21][C:22]4[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=4)=[N:18][CH:19]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1)([CH3:34])=[CH2:33]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 670832785-Bromo-2-[4-[2-(4-methanesulfonylphenoxymethyl)pyridin-5-yl]piperidin-1-yl]pyrimidine

Product 1

HCID 670832375-Isopropenyl-2-[4-[2-(4-methanesulfonylphenoxymethyl)pyridin-5-yl]piperidin-1-yl]pyrimidineYield 79.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-bromo-2-[4-[2-(4-methanesulfonylphenoxymethyl)pyridin-5-yl]piperidin-1-yl]pyrimidine (Example 57) (31 mg, 0.062 mmol) and isopropenylboronic acid pinacol ester (23 μL, 0.124 mmol) in dry N,N-dimethylformamide (0.3 mL) was added [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium (complex with dichloromethane) (1 mg, 0.012 mmol) and cesium carbonate (40 mg, 0.124 mmol). The mixture was stirred at 90° C. overnight under N2, allowed to cool to room temperature, diluted with water (1 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2) to give the title compound as a white crystal (23 mg, yield 78%).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-3f26bf8f931a4c0981a65a18feb1db66
Source dataset
uspto-grants-2013_09
Patent number
US08536176B2

Linked notes

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