Triethylamine → 1-[4-(3-acetyl-6-bromo-1-oxo-4-phenyl-1H-isoquinolin-2-ylmethyl)benzenesulfonyl]piperidine-4-carboxylic Acid Ethyl Ester

HRID 750313Notes

Reaction equation

HRID 750313 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].[CH2:22]([O:24][C:25]([CH:27]1[CH2:32][CH2:31][N:30]([S:33]([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][NH2:43])=[CH:38][CH:37]=2)(=[O:35])=[O:34])[CH2:29][CH2:28]1)=[O:26])[CH3:23].C(N(CC)CC)C>CO>[CH2:22]([O:24][C:25]([CH:27]1[CH2:32][CH2:31][N:30]([S:33]([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][N:43]3[C:4]([C:1](=[O:3])[CH3:2])=[C:13]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:12]4[C:7](=[CH:8][CH:9]=[C:10]([Br:20])[CH:11]=4)[C:6]3=[O:5])=[CH:38][CH:37]=2)(=[O:34])=[O:35])[CH2:29][CH2:28]1)=[O:26])[CH3:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 230605293-Acetyl-6-bromo-4-phenylisochromen-1-oneHCID 691577331-(4-Aminomethylbenzenesulfonyl)piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 691567501-[4-(3-acetyl-6-bromo-1-oxo-4-phenyl-1H-isoquinolin-2-ylmethyl)benzenesulfonyl]piperidine-4-carboxylic Acid Ethyl EsterYield 14%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[Step 3] To a solution of 3-acetyl-6-bromo-4-phenylisochromen-1-one (343 mg) in methanol (20 ml) were added 1-(4-aminomethylbenzenesulfonyl)piperidine-4-carboxylic acid ethyl ester (979 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 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=7/3→2/3) to give the title compound (91 mg, 14%). 1H-NMR (CDCl3) δ: 1.21 (3H, t, J=7.0 Hz), 1.37 (3H, s), 1.65-2.01 (4H, m), 2.11 (1H, m), 2.38-2.56 (2H, m), 3.50-3.66 (2H, m), 4.09 (2H, q, J=7.0 Hz), 5.47 (2H, s), 7.24-7.50 (8H, m), 7.67-7.76 (3H, m), 8.41 (1H, d, J=8.4 Hz).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. custompartitioned 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=7/3→2/3)

Sources & evidence

ORD record
ord-04e8f3d37417430f847ad69de520b3fc
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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