Tetrahydrofuran → HCID 66787865, compound

HRID 1623517Notes

Reaction equation

HRID 1623517 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[C:12](=[O:18])[CH2:11]3)[CH:5]=[N:6][CH:7]=1.[CH:19]1([B-](F)(F)F)[CH2:21][CH2:20]1.[K+].C1COCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>ClCCl.O>[CH:19]1([C:2]2[CH:3]=[C:4]([C:8]3[CH:9]=[C:10]4[C:14](=[CH:15][CH:16]=3)[N:13]([CH3:17])[C:12](=[O:18])[CH2:11]4)[CH:5]=[N:6][CH:7]=2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 23697338Potassium cyclopropyltrifluoroborateHCID 66788512HCID 66788512, compound

Product 1

HCID 66787865HCID 66787865, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
125 °C

Procedure

To 5-(5-bromo-pyridin-3-yl)-1-methyl-1,3-dihydro-indol-2-one, prepared as described in Example 21, (100 mg, 0.330 mmol) was added potassium cyclopropyltrifluoroborate (50 mg, 0.35 mmol), THF (2 mL), water, (0.66 mL), and tripotassium phosphate (245 mg, 1.155 mmol). The reaction mixture was degassed and placed under an argon atmosphere, and then [1,1′-bis(diphenylphospihino)-ferrocene]-dichloropalladium(II) complexed with dichloromethane (CAS#72287-26-4 13.5 mg, 0.016 mmol) was added. The reaction vessel was sealed and was heated by microwave irradiation at 125° C. for 85 minutes. The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%) to afford 5-(5-cyclopropyl-pyridin-3-yl)-1-methyl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 265.1345 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.72-0.89 (m, 2H), 1.03-1.19 (m, 2H), 1.85-2.11 (m, 1H), 3.27 (s, 3H), 3.61 (s, 2H), 6.92 (d, J=8.1 Hz, 1H), 7.39-7.61 (m, 3H), 8.38 (d, J=1.8 Hz, 1H), 8.60 (d, J=2.0 Hz, 1H).

Workup

  1. customThe reaction mixture was degassed
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationfiltered through glass wool
  6. additionThe filtrate was further diluted with saturated aqueous sodium bicarbonate
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted two times with dichloromethane
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%)

Sources & evidence

ORD record
ord-ef093fe0e3b74f969f05c386c690afe3
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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