Hydrochloric Acid → N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(3-methyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride

HRID 68971Notes

Reaction equation

HRID 68971 reaction equation
[ClH:1].[CH2:2]([N:4]1[C:10](=[O:11])[C:9]([CH3:13])([CH3:12])[C:8](=[O:14])[N:7]([CH3:15])[C:6]2[CH:16]=[C:17]([CH2:20][N:21]([CH2:35][CH2:36][C:37]3[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=3)[C:22](=[O:34])[CH2:23][N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[NH:26][C:25]3=[O:33])[CH:18]=[CH:19][C:5]1=2)[CH3:3].[C:43](=O)([O-])[O-].[Cs+].[Cs+].CI.Cl>C(O)C.CC(O)C.O.CN(C=O)C>[ClH:1].[CH2:2]([N:4]1[C:10](=[O:11])[C:9]([CH3:13])([CH3:12])[C:8](=[O:14])[N:7]([CH3:15])[C:6]2[CH:16]=[C:17]([CH2:20][N:21]([CH2:35][CH2:36][C:37]3[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=3)[C:22](=[O:34])[CH2:23][N:24]3[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[N:26]([CH3:43])[C:25]3=[O:33])[CH:18]=[CH:19][C:5]1=2)[CH3:3]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 70656544N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride

Product 1

HCID 66960572N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(3-methyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochlorideYield 75.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Procedure

N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride (0.26 g), cesium carbonate (0.43 g), and methyl iodide (0.04 ml) were added to DMF (5 ml), and the mixture was stirred at room temperature for 1 days. Water was added to the reaction mixture, and stirred for 1 hour, followed by extraction with ethyl acetate. The organic layer was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethylacetate:methanol=85:15). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution (0.44 ml) was added to a 2-propanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (0.20 g) as a white powder.

Workup

  1. stirringstirred for 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. customcondensed under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (ethylacetate:methanol=85:15)
  5. customcondensed under reduced pressure
  6. stirringthe liquid was stirred at room temperature
  7. concentrationconcentrated under reduced pressure
  8. additionEthanol and ether were added to the residue
  9. customThe precipitated insoluble matter was separated
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-05ecfbe3117544ef85762f35e7a3dc23
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Reaction notes

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