Methyl chloroformate → Methyl [4-[(6-bromo-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl]phenyl]sulfonylcarbamate

HRID 750350Notes

Reaction equation

HRID 750350 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1)[C:6]([C:24](=[O:27])[CH2:25][CH3:26])=[C:5]2[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C.[C:41](Cl)(=[O:44])[O:42][CH3:43]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([S:20]([NH:23][C:41](=[O:44])[O:42][CH3:43])(=[O:21])=[O:22])=[CH:18][CH:19]=1)[C:6]([C:24](=[O:27])[CH2:25][CH3:26])=[C:5]2[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 69156329HCID 69156329, compound

Product 1

HCID 86599570Methyl [4-[(6-bromo-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl]phenyl]sulfonylcarbamate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(6-bromo-1-oxo-4-phenyl-3-propionyl-1H-isoquinolin-2-ylmethyl)benzenesulfonamide (0.2 g), triethylamine (0.11 ml), 4-dimethylaminopyridine (23 mg) and methylene chloride (2.0 ml) was added methyl chlorocarbonate (35 μl) at room temperature with stirring, and the mixture was stirred at the same temperature for 1 hr. After the completion of the reaction, the reaction mixture was washed with 1N hydrochloric acid, and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by medium pressure preparative LC (hexane/ethyl acetate=3/1-1/1), crystallized from hexane/ethyl acetate=3/2 to give the title compound (0.15 g) as colorless crystals. 1H NMR (CDCl3) δ: 0.48 (3H, t, J=6.9 Hz), 1.69 (2H, q, J=6.9 Hz), 3.68 (3H, s), 5.38 (2H, s), 7.23-7.32 (2H, m), 7.41 (2H, d, J=8.7 Hz), 7.44-7.53 (5H, m), 7.69 (1H, dd, J=2.1, 8.4 Hz) 7.98 (2H, d, J=8.7 Hz), 8.40 (1H, d, J=8.4 Hz).

Workup

  1. stirringthe mixture was stirred at the same temperature for 1 hr
  2. customAfter the completion of the reaction
  3. washthe reaction mixture was washed with 1N hydrochloric acid
  4. dry with materialthe organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by medium pressure preparative LC (hexane/ethyl acetate=3/1-1/1)
  7. customcrystallized from hexane/ethyl acetate=3/2

Sources & evidence

ORD record
ord-a0d0f1c7a4364e21865b3cb6ec9e2530
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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