Dimethylformamide → N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamide

HRID 2196078Notes

Reaction equation

HRID 2196078 reaction equation
C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.I[CH2:13][CH2:14][CH2:15][N:16]([CH2:29][CH2:30][N:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]1=[O:41])[S:17]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N+:26]([O-:28])=[O:27])(=[O:19])=[O:18].[CH2:42]([N:44]1[C:50](=[O:51])[C:49]([CH3:53])([CH3:52])[C:48](=[O:54])[N:47]([CH3:55])[C:46]2[CH:56]=[C:57]([OH:60])[CH:58]=[CH:59][C:45]1=2)[CH3:43]>C(OCC)(=O)C>[CH2:42]([N:44]1[C:50](=[O:51])[C:49]([CH3:53])([CH3:52])[C:48](=[O:54])[N:47]([CH3:55])[C:46]2[CH:56]=[C:57]([O:60][CH2:13][CH2:14][CH2:15][N:16]([CH2:29][CH2:30][N:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:32]3=[O:41])[S:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[N+:26]([O-:28])=[O:27])(=[O:19])=[O:18])[CH:58]=[CH:59][C:45]1=2)[CH3:43]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 68673067HCID 68673067, compoundHCID 686733851-Ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 68675475N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamideYield 69.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Potassium carbonate (0.22 g, 1.6 mmol) was added to a DMF solution (10 ml) of N-(3-iodopropyl)-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamide (0.57 g, 1.05 mmol) and 1-ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.33 g, 1.26 mmol), and stirred at room temperature overnight. The reaction mixture was added to ice water, and extraction with ethyl acetate was performed. The organic layer was washed with 1N-sodium hydroxide aqueous solution and water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1→0:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 0.49 g (yield: 69%) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamide as a white amorphous solid.

Workup

  1. washThe organic layer was washed with 1N-sodium hydroxide aqueous solution and water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1→0:1)
  5. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-91504807af9b4bf9856a9db5c6ed2525
Source dataset
uspto-grants-2012_12
Patent number
US08338406B2

Reaction notes

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