Potassium Carbonate → 4-(5-Methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoic acid

HRID 717109Notes

Reaction equation

HRID 717109 reaction equation
Cl[C:2]1[NH:3][C:4](=[O:13])[C:5]2[C:10]([CH:11]=1)=[C:9]([CH3:12])[CH:8]=[CH:7][CH:6]=2.[C:14]([O-:17])([O-])=[O:15].[K+].[K+]>COCCOC.CCO.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:12][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[CH:11]=[C:2]([C:5]1[CH:10]=[CH:9][C:8]([C:14]([OH:17])=[O:15])=[CH:7][CH:6]=1)[NH:3][C:4]2=[O:13]

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 229310333-Chloro-5-methyl-2H-isoquinolin-1-one

Product 1

HCID 898128824-(5-Methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoic acidYield 79.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

3-Chloro-5-methyl-2H-isoquinolin-1-one (50 mg, 0.26 mmol), 4-carboxybenezeneboronic acid (64 mg, 0.39 mmol), K2CO3 (73 mg, 0.52 mmol) and Pd(dppf)Cl2 (11 mg, 0.013 mmol) in DME/EtOH/H2O 4:0.5:1 (2.75 mL) were added to a microwave vial and the reaction mixture purged with N2 for 10 min. The reaction mixture was irradiated using a microwave (300 W, 120° C., 2 h). The reaction mixture was concentrated in vacuo, water added and the mixture acidified to pH2 with 0.2M HCl aq. A brown solid precipiated from the solution which was filtered and dried in vacuo, dissolved in DMF and passed through a Si-thiol cartridge, eluting with DMF (4× column volumes) and the solvent removed in vacuo. The resulting solid was triturated with MeOH, filtered and dried to give 4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoic acid as a beige solid (29 mg, 40%).

Workup

  1. customthe reaction mixture purged with N2 for 10 min
  2. customThe reaction mixture was irradiated
  3. customa microwave (300 W, 120° C., 2 h)
  4. concentrationThe reaction mixture was concentrated in vacuo, water
  5. additionadded
  6. filtrationwas filtered
  7. customdried in vacuo
  8. dissolutiondissolved in DMF
  9. washeluting with DMF (4× column volumes)
  10. customthe solvent removed in vacuo
  11. customThe resulting solid was triturated with MeOH
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-633fbaa8edd74f57bb4e4f828591e6c8
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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