Water → 7-Chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

HRID 1910682Notes

Reaction equation

HRID 1910682 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[NH:6][C:7](=[O:21])[CH:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[NH:9][C:10](=[O:11])[C:4]=2[CH:3]=1.Cl[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[C:7](=[O:21])[CH:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[NH:9][C:10](=[O:11])[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 672831157-Chloro-3-(2-chlorophenethyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Product 1

HCID 672826197-Chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dioneYield 72.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-Chloro-3-(2-chlorophenethyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (1.0 g, 1 eq), 1-(chloromethyl)-4-methoxybenzene (448 mg, 1 eq), and potassium carbonate (1.19 g, 3 eq) were suspended in DMF (11.5 mL), and the mixture was stirred at room temperature overnight. Water was then added and the mixture was stirred for 30 minutes. The solid was collected by filtration, and the solid was returned to a flask and concentrated from toluene to remove water. The crude material was purified by chromatography (gradient: 9:1 hexanes:EtOAc to 1:1 hexanes:EtOAc) yielding a white solid (970 mg, 72% yield). 1H-NMR (300 MHz, DMSO-d6) δ 8.90 (d, 1H), 7.60-7.50 (m, 3H), 7.38-7.17 (m, 4H), 6.97 (d, 2H), 6.78 (d, 2H), 5.32 (d, 1H), 4.81 (d, 1H), 3.80 (m, 1H), 3.65 (s, 3H), 2.74 (t, 2H), 2.10 (m, 1H), 1.90 (m, 1H). MS (ES+) m/z 490.9 (M+Na).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. filtrationThe solid was collected by filtration
  3. customthe solid was returned to a flask
  4. concentrationconcentrated from toluene
  5. customto remove water
  6. customThe crude material was purified by chromatography (gradient: 9:1 hexanes:EtOAc to 1:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-14171ce3c38b422597005ef3dfce3037
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

Loading…