Potassium Acetate → 7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-5-nitroisoquinolin-1(2H)-one

HRID 577598Notes

Reaction equation

HRID 577598 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1.[CH3:16][N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[N:18]1.CCCCP(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2.C([O-])(=O)C.[K+]>CC(O)(CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:16][N:17]1[C:21]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][NH:8][C:9]3=[O:12])=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=2)=[C:20]([CH3:22])[N:19]=[N:18]1

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 152571421,4-Dimethyl-1H-1,2,3-triazoleHCID 825721717-bromo-5-nitroisoquinolin-1(2H)-one

Product 1

HCID 867238257-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-5-nitroisoquinolin-1(2H)-oneYield 60%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 7-bromo-5-nitroisoquinolin-1(2H)-one (293b, 4.00 g, 14.9 mmol), 1,4-dimethyl-1H-1,2,3-triazole (2.17 g, 22.3 mmol), palladium acetate (334 mg, 1.49 mmol), CatacXiumA (butyl di-1-adamantylphosphine) (1.10 g, 2.97 mmol), and potassium acetate (7.30 g, 74.3 mmol) in 2-methyl-2-butanol (100 mL) was degassed with nitrogen, and heated at 120° C. in a sealed tube overnight. After cooling down room temperature, the reaction mixture was partitioned between ethyl acetate (300 mL) and water (300 mL). The organic phase was separated, washed with brine (1×300 mL), dried over sodium sulfate, concentrated to dryness, and purified by silica gel chromatography (eluting with a gradient of 0%-10% methanol in ethyl acetate), affording 7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-5-nitroisoquinolin-1(2H)-one (293c, 2.55 g, 60% yield) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 11.95 (br. s., 1H), 8.57 (s, 2H), 7.55 (d, J=5.38 Hz, 1H), 6.98 (d, J=7.34 Hz, 1H), 4.00 (s, 3H), 2.29 (s, 3H). MS: 284 [M−1].

Workup

  1. customwas degassed with nitrogen
  2. temperatureAfter cooling down room temperature
  3. customthe reaction mixture was partitioned between ethyl acetate (300 mL) and water (300 mL)
  4. customThe organic phase was separated
  5. washwashed with brine (1×300 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness
  8. custompurified by silica gel chromatography (
  9. washeluting with a gradient of 0%-10% methanol in ethyl acetate),

Sources & evidence

ORD record
ord-4af0cc07c1024da7ace15f6b0501fcb9
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

Loading…