Triethylamine → methyl 4-(3-acetyl-6-bromo-1-oxo-4-phenyl-1H-isoquinolin-2-ylmethyl)benzoate

HRID 750311Notes

Reaction equation

HRID 750311 reaction equation
[C:1]([C:4]1[O:5][C:6](=O)[C:7]2[C:12]([C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:11][C:10]([Br:20])=[CH:9][CH:8]=2)(=[O:3])[CH3:2].Cl.[CH3:23][O:24][C:25](=[O:34])[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][NH2:33])=[CH:28][CH:27]=1.C(N(CC)CC)C>CO>[CH3:23][O:24][C:25](=[O:34])[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[C:4]([C:1](=[O:3])[CH3:2])=[C:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([Br:20])[CH:11]=3)[C:6]2=[O:5])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochlorideHCID 230605293-Acetyl-6-bromo-4-phenylisochromen-1-one

Product 1

HCID 69156099methyl 4-(3-acetyl-6-bromo-1-oxo-4-phenyl-1H-isoquinolin-2-ylmethyl)benzoateYield 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[Step 2] To a solution of 3-acetyl-6-bromo-4-phenyl-isochromen-1-one (1.03 g) in methanol (100 ml) were added 4-aminomethyl-benzoic acid methyl ester hydrochloride (3.02 g) and triethylamine (4.2 ml) and the mixture was stirred at room temperature for 18 hrs. The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract 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=19/1→3/1) to give the title compound (220 mg, 15%).

Workup

  1. customThe solvent was evaporated under reduced pressure, 1N hydrochloric acid
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. customdried
  6. additionby adding sodium sulfate
  7. customThe solvent was evaporated under reduced pressure, 4N hydrochloric acid ethyl acetate solution (5 ml)
  8. additionwas added to the obtained residue
  9. stirringthe mixture was stirred at room temperature for 10 hrs
  10. customThe solvent was evaporated under reduced pressure, water
  11. additionwas added
  12. extractionthe mixture was extracted with ethyl acetate
  13. washThe extract was washed with saturated sodium hydrogen carbonate solution and saturated brine
  14. customdried
  15. additionby adding sodium sulfate
  16. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1)

Sources & evidence

ORD record
ord-1db1a20af399479da0d5b7d0364745d8
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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