Cesium carbonate → HCID 86691825, compound

HRID 1616217Notes

Reaction equation

HRID 1616217 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[C:5]#[N:6].C([O-])(=O)C.[K+].Cl[C:17]1[N:22]=[C:21]2[N:23]([CH3:32])[C:24](=[O:31])[N:25]([CH2:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:20]2=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CO.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[CH3:28][C:27]([CH3:30])([CH3:29])[CH2:26][N:25]1[C:20]2[C:21](=[N:22][C:17]([C:2]3[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=3[CH3:10])[C:5]#[N:6])=[CH:18][CH:19]=2)[N:23]([CH3:32])[C:24]1=[O:31]

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 140048403-Bromo-4-methylbenzonitrileHCID 86691826HCID 86691826, compound

Product 1

HCID 86691825HCID 86691825, compound

Reagents, catalysts & solvents 5

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418851HCID 178418851, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a microwave vial, 3-bromo-4-methylbenzonitrile (250 mg, 1.28 mmol), Bispinnacoloto(diboron) (356 mg, 1.4 mmol), Potassium Acetate (560 mg, 5.74 mmol), and Bis(diphenylphosphino)ferrocene dicholoropalladium (180 mg, 0.25 mmol) was added under nitrogen and suspended in dioxane (2.5 ml). The mixture was refluxed at 90° C. overnight, and showed the intermediate boronic ester. The reaction was cooled to room temperature and to the reaction mixture was added 14-1 (191 mg, 0.76 mmol), cesium carbonate (830 mg, 2.6 mmol), bis(tri-t-butylphosphine)palladium(0) (65 mg, 0.13 mmol) and water (0.7 mL). The mixture was refluxed at 90° C. overnight, at the desired coupled product was observed by LC/MS. The mixture was diluted with methanol and purified using reverse phase chromatography (10-100%, 0.1% TFA in H2O/Acetonitrile); the desired fractions were collected and concentrated to produce 3-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]-4-methylbenzonitrile (15-1). HRMS (M+H)+: observed=335.1865, calculated=335.1866.

Workup

  1. temperatureThe reaction was cooled to room temperature and to the reaction mixture
  2. temperatureThe mixture was refluxed at 90° C. overnight
  3. custompurified
  4. customthe desired fractions were collected
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-644f5614c8f6410fb753247aba3a867b
Source dataset
uspto-grants-2014_07
Patent number
US08765784B2

Reaction notes

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