Triethylamine → 6-bromo-1-oxo-4-phenyl-2-(4-[1,2,3]thiadiazole-4-ylbenzyl)-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750320Notes

Reaction equation

HRID 750320 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:6][C:7](=O)[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].[S:23]1[CH:27]=[C:26]([C:28]2[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=2)[N:25]=[N:24]1.C(N(CC)CC)C>CO>[CH3:1][O:2][C:3]([C:5]1[N:33]([CH2:32][C:31]2[CH:30]=[CH:29][C:28]([C:26]3[N:25]=[N:24][S:23][CH:27]=3)=[CH:35][CH:34]=2)[C:7](=[O:6])[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

5

Reactant 3

HCID 8471TriethylamineHCID 27372881-[4-(1,2,3-Thiadiazol-4-Yl)phenyl]methanamineHCID 66990710Methyl 6-bromo-1-oxo-4-phenyl-1H-isochromene-3-carboxylate

Product 1

HCID 691560326-bromo-1-oxo-4-phenyl-2-(4-[1,2,3]thiadiazole-4-ylbenzyl)-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-bromo-1-oxo-4-phenyl-1H-isochromen-3-carboxylic acid methyl ester (359 mg) in methanol (20 ml) were added 4-[1,2,3]thiadiazol-4-ylbenzylamine (956 mg) and triethylamine (1.4 ml) and the mixture was stirred at room temperature for 72 hrs. The solvent was evaporated under reduced pressure, and the residue was partitioned between 1N hydrochloric acid and ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure, 4N hydrochloric acid ethyl acetate solution (5 ml) was added to the obtained residue, and the mixture was stirred at room temperature for 10 hrs. The solvent was evaporated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium hydrogen carbonate solution and saturated brine and dried by adding sodium sulfate. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/1→1/1) to give the title compound (80 mg, 15%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was partitioned between 1N hydrochloric acid and ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. customdried
  5. additionby adding sodium sulfate
  6. customThe solvent was evaporated under reduced pressure, 4N hydrochloric acid ethyl acetate solution (5 ml)
  7. additionwas added to the obtained residue
  8. stirringthe mixture was stirred at room temperature for 10 hrs
  9. customThe solvent was evaporated under reduced pressure, water
  10. additionwas added
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe extract was washed with saturated sodium hydrogen carbonate solution and saturated brine
  13. customdried
  14. additionby adding sodium sulfate
  15. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/1→1/1)

Sources & evidence

ORD record
ord-372ac2800f16404aafe621f82eba7a99
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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