Thioglycolic Acid → 1-Ethyl-3,3,5-trimethyl-7-{3-[2-(1-oxo-1H-isoquinolin-2-yl)ethylamino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

HRID 68988Notes

Reaction equation

HRID 68988 reaction equation
[OH-].[Li+].C(O)(=O)CS.CN(C=O)C.[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([CH2:31][CH2:32][CH2:33][N:34]([CH2:47][CH2:48][N:49]3[CH:58]=[CH:57][C:56]4[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=4)[C:50]3=[O:59])S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH:29]=[CH:30][C:16]1=2)[CH3:14]>O>[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([CH2:31][CH2:32][CH2:33][NH:34][CH2:47][CH2:48][N:49]3[CH:58]=[CH:57][C:56]4[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=4)[C:50]3=[O:59])[CH:29]=[CH:30][C:16]1=2)[CH3:14]

Participants

6

Reactant 4

HCID 1133Thioglycolic AcidHCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 66960684HCID 66960684, compound

Product 1

HCID 706569721-Ethyl-3,3,5-trimethyl-7-{3-[2-(1-oxo-1H-isoquinolin-2-yl)ethylamino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dioneYield 68.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Lithium hydroxide (3.2 g), and thioglycolic acid (2.4 ml) were added to a DMF solution (27.4 ml) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)propyl]-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamide (4.56 g). The mixture was stirred at room temperature for 1 hour. The reaction mixture was condensed under reduced pressure. Water was added to the residue, followed by extraction using dichloromethane. The organic layer was washed with water and saturated saline, dried with magnesium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1). The purified product was condensed under reduced pressure to produce the title compound (2.24 g) as a yellow oil.

Workup

  1. customcondensed under reduced pressure
  2. extractionfollowed by extraction
  3. washThe organic layer was washed with water and saturated saline
  4. dry with materialdried with magnesium sulfate, and condensed under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1)
  6. customcondensed under reduced pressure

Sources & evidence

ORD record
ord-badb09cd37d441ab95f32fa66d52b37c
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Reaction notes

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