Sodium Iodide → 1-Ethyl-3,3,5-trimethyl-7-[3-(2-phenylpiperidin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride

HRID 69054

Reaction equation

HRID 69054 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[C:9]1([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][NH:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Cl:21][CH2:22][CH2:23][CH2:24][O:25][C:26]1[CH:43]=[CH:42][C:29]2[N:30]([CH2:40][CH3:41])[C:31](=[O:39])[C:32]([CH3:38])([CH3:37])[C:33](=[O:36])[N:34]([CH3:35])[C:28]=2[CH:27]=1.C(OC(=O)C)C.Cl>C(OCC)(=O)C.O.CN(C=O)C>[ClH:21].[CH2:40]([N:30]1[C:31](=[O:39])[C:32]([CH3:37])([CH3:38])[C:33](=[O:36])[N:34]([CH3:35])[C:28]2[CH:27]=[C:26]([O:25][CH2:24][CH2:23][CH2:22][N:16]3[CH2:17][CH2:18][CH2:19][CH2:20][CH:15]3[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:43]=[CH:42][C:29]1=2)[CH3:41]

Participants

9

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 1030202-PhenylpiperidineHCID 21866389Hydrogen chloride-ethyl acetateHCID 686732537-(3-Chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 669612001-Ethyl-3,3,5-trimethyl-7-[3-(2-phenylpiperidin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochlorideYield 27.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Potassium carbonate (0.54 g), sodium iodide (0.21 g), and 2-phenyl piperidine (0.23 g) were added to a DMF solution (15 ml) of 7-(3-chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.44 g). The mixture was stirred at 70° C. for 5 hours. The reaction mixture was cooled to room temperature. Water was added thereto, followed by extraction by ethyl acetate. The organic layer was washed with water and then with saturated saline, and dried with anhydrous magnesium sulfate. After condensation under reduced pressure, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:1). The purified product was condensed under reduced pressure. A 4N-Hydrogen chloride ethyl acetate solution (0.2 ml) was added to an ethyl acetate solution (10 ml) of the residue, which was stirred at room temperature. The liquid was condensed to dryness under reduced pressure to give the title compound (0.18 g) as a white amorphous solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction by ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialwith saturated saline, and dried with anhydrous magnesium sulfate
  5. customAfter condensation under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:1)
  7. customcondensed under reduced pressure
  8. stirringwas stirred at room temperature
  9. customcondensed to dryness under reduced pressure

Sources & evidence

ORD record
ord-2596dfbb3adc47489b70a46d9f61cf27
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Linked notes

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