Tetrahydrofuran → HCID 66793835, compound

HRID 1623529Notes

Reaction equation

HRID 1623529 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:9]([Cl:19])=[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:20]1([B-](F)(F)F)[CH2:22][CH2:21]1.[K+].C1COCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>ClCCl.C(=O)(O)[O-].[Na+]>[Cl:19][C:9]1[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([CH:20]3[CH2:22][CH2:21]3)[CH:3]=2)=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:18])[N:13]2[CH3:17]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 23697338Potassium cyclopropyltrifluoroborateHCID 66788274HCID 66788274, compound

Product 1

HCID 66793835HCID 66793835, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
125 °C

Procedure

To 5-(5-bromo-pyridin-3-yl)-4-chloro-1-methyl-1,3-dihydro-indol-2-one prepared as described in Example 28, (85 mg, 0.25 mmol) was added potassium cyclopropyltrifluoroborate (41 mg, 0.38 mmol), THF (2 mL) water, (0.66 mL), and tripotassium phosphate (187 mg, 0.88 mmol). The reaction mixture was degassed and placed under an argon atmosphere, and then (1,1′-bis(diphenylphosphino)-ferrocenel-dichloropalladium(II) complexed with dichloromethane (CAS#72287-26-4 10.3 mg, 0.013 mmol) was added. The reaction vessel was sealed and was heated by microwave irradiation at 125° C. for 4 h. The reaction mixture was cooled to room temperature and diluted with dichloromethane and 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 through a pad of Celite®, and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%) to afford 4-chloro-5-(5-cyclopropyl-pyridin-3-yl)-1-methyl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 299.0955 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.78-0.82 (m, 2H), 1.01-1.18 (m, 2H), 1.94-2.04 (m, 1H), 3.26 (s, 3H), 3.61 (s, 2H), 6.83 (d, J=7.8 Hz, 1H), 7.26-7.31 (m, 1H), 7.44 (br. s., 1H), 8.36-8.54 (m, 2H).

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. customthe layers were separated
  6. extractionThe aqueous layer was extracted two times with dichloromethane
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered through a pad of Celite®
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%)

Sources & evidence

ORD record
ord-9dd8a901265f4fa49d0bfa64a2ad1908
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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