Water → 2-(benzo[2,1,3]thiadiazol-5-ylmethyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750178Notes

Reaction equation

HRID 750178 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][C:7](=[O:22])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([Br:21])=[CH:10][CH:9]=2)=[O:4].[H-].[Na+].Br[CH2:26][C:27]1[CH:35]=[CH:34][C:30]2=[N:31][S:32][N:33]=[C:29]2[CH:28]=1.O>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:26][C:27]2[CH:35]=[CH:34][C:30]3=[N:31][S:32][N:33]=[C:29]3[CH:28]=2)[C:7](=[O:22])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([Br:21])=[CH:10][CH:9]=2)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5910045-(Bromomethyl)-2,1,3-benzothiadiazoleHCID 691573826-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

Product 1

HCID 691559912-(benzo[2,1,3]thiadiazol-5-ylmethyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester (600 mg) in DMF (6 ml) was added sodium hydride (60% in oil, 74 mg) under ice-cooling, and the mixture was allowed to warm to room temperature and stirred for 1 hr. To the reaction mixture was added 5-bromomethylbenzo[2,1,3]thiadiazole (460 mg) at room temperature, and the mixture was stirred for 2 hrs. Water was added to the reaction mixture and crystals were collected by filtration, washed with ethyl acetate. The filtrate was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine and dried. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethyl acetate. The crystals were collected by filtration, combined with the crystals obtained earlier, and subjected to silica gel column chromatography (THF) and further to recrystallization (THF-ethyl acetate) to give the title compound (450 mg).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 2 hrs
  3. filtrationwere collected by filtration
  4. washwashed with ethyl acetate
  5. extractionThe filtrate was extracted with ethyl acetate
  6. washthe organic layer was washed with water and saturated brine
  7. customdried
  8. customThe solvent was evaporated under reduced pressure
  9. customthe obtained residue was crystallized from ethyl acetate
  10. filtrationThe crystals were collected by filtration
  11. customobtained earlier
  12. customsubjected to silica gel column chromatography (THF) and further to recrystallization (THF-ethyl acetate)

Sources & evidence

ORD record
ord-24461e9f3dd04c94b47cbfc852b3901f
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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