Hydrogen Bromide → 5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 577603Notes

Reaction equation

HRID 577603 reaction equation
N[C:2]1[CH:11]=[C:10]([C:12]2[N:16]([CH3:17])[N:15]=[N:14][C:13]=2[CH3:18])[C:9]([Cl:19])=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][C:7]2=[O:20].[BrH:21].N([O-])=O.[Na+].[OH-].[Na+]>O1CCCC1.[Cu]Br>[Br:21][C:2]1[CH:11]=[C:10]([C:12]2[N:16]([CH3:17])[N:15]=[N:14][C:13]=2[CH3:18])[C:9]([Cl:19])=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][C:7]2=[O:20]

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 14798Sodium HydroxideHCID 23668193Sodium NitriteHCID 867238295-amino-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867238305-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 16.5%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-amino-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (293 g, 300 mg, 1.03 mmol) in tetrahydrofuran (5 mL) chilled in an ice-water bath was added 40% aqueous hydrobromic acid (6.86 g, 33.93 mmol). The mixture was allowed to stir at room temperature for three hours, and then cooled again to 0° C. Copper (I) bromide (295 mg, 2.06 mmol) was added, followed by sodium nitrite (78 mg, 1.13 mmol), and the resulting mixture stirred at 0° C. for two hours. The mixture was neutralized with solid sodium hydroxide and extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography to give 5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (293h, 60 mg, 16.5% yield) as a white solid.

Workup

  1. temperaturecooled again to 0° C
  2. stirringthe resulting mixture stirred at 0° C. for two hours
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-e7373195ed4a40e98f54cde9beba93eb
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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