Potassium Carbonate → HCID 89977510, compound

HRID 1424067Notes

Reaction equation

HRID 1424067 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][O:23][Si](C(C)(C)C)(C)C)([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Cl:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][C:33]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>C(COC)OC.O.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>[Cl:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][C:33]=1[C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][OH:23])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 120670644-Chloropyridine-3-boronic acid, pinacol esterHCID 86712858HCID 86712858, compound

Product 1

HCID 89977510HCID 89977510, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of the compound (508 mg, 1.0 mmol) obtained in Example 16-4), 4-chloropyridine-3-boronic acid pinacol ester (366 mg, 1.5 mmol), tetrakis(triphenylphosphine)palladium(0) (231 mg, 0.2 mmol), and potassium carbonate (276 mg, 2 mmol) in dimethoxyethane (4 mL) and water (1 mL) was stirred at 130° C. for 1.5 h under microwave irradiation. The reaction mixture was cooled to room temperature, saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 20:80, gradient). This partially purified product was dissolved in a solution of 4 M hydrochloric acid (1,4-dioxane solution, 1 mL) in methanol (4 mL), and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (135 mg, 32%) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 20:80, gradient)
  7. dissolutionThis partially purified product was dissolved in a solution of 4 M hydrochloric acid (1,4-dioxane solution, 1 mL) in methanol (4 mL)
  8. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate
  9. additionwas added to the residue
  10. extractionthe mixture was extracted with dichloromethane
  11. washthe organic layer was washed with saturated sodium chloride solution
  12. dry with materialdried with anhydrous sodium sulfate
  13. filtrationAfter filtration
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient)

Sources & evidence

ORD record
ord-306b8d562d0540b284e36ef64097b0f9
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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