Ethanol → 8-(Pyridin-4-yl)isoquinolin-1(2H)-one
Reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH:8]=[CH:7]2.C(O)C.C(=O)(O)[O-].[Na+].[N:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1>ClCCl.O.C(Cl)Cl.CO.C1(C)C=CC=CC=1>[N:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[C:10](=[O:12])[NH:9][CH:8]=[CH:7]3)=[CH:23][CH:22]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 130 °C
Procedure
A reaction tube was charged with 8-bromoisoquinolin-1(2H)-one (1 g, 4.46 mmol) and a mixture of 3 mL of ethanol and 3 mL of toluene under argon. To this, an aqueous sodium bicarbonate solution (2 M, 710 mg, 3.35 mL, 6.69 mmol) was added and then pyridin-4-ylboronic acid (549 mg, 4.46 mmol). Then, tetrakis(triphenyl-phosphine)palladium (516 mg, 4.46 mmol) was added. The reaction mixture was heated in a Biotage microwave at 130° C. for 30 min. The reaction was monitored by TLC (DCM/methanol=9:1). After completion of the reaction, the reaction mixture was mixed with water and dichloromethane. The solid was sucked off. The organic phase was washed with an aqueous NaHCO3 solution, brine, dried (MgSO4) and evaporated. The residue was taken up with EA and the precipitate was sucked off. The crude product was purified by chromatography (Campanion normal phase, gradient elution, using 3-10% DCM in methanol) to yield 465 mg (46.9%) of the title compound.
Workup
- customAfter completion of the reaction
- washThe organic phase was washed with an aqueous NaHCO3 solution, brine
- dry with materialdried (MgSO4)
- customevaporated
- customThe crude product was purified by chromatography (Campanion normal phase, gradient elution, using 3-10% DCM in methanol)
Sources & evidence
- ORD record
- ord-053402467c59482ab57adb00dc197f5d
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273068B2
Reaction notes
Loading…