N,N-Dimethylaniline → 5,7-Dichloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 1910683Notes

Reaction equation

HRID 1910683 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]2[N:6]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=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)[C:4]=2[CH:3]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:44])=O>C1(C)C=CC=CC=1>[Cl:44][C:10]1[C:4]2[CH:3]=[C:2]([Cl:1])[CH:32]=[CH:31][C:5]=2[N:6]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[C:7](=[O:21])[CH:8]([CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:20])[N:9]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 672826197-Chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Product 1

HCID 672834205,7-Dichloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

7-Chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (950 mg) was dissolved in toluene (20 mL) and then N,N-dimethylaniline (564 mg, 2.3 eq) was added followed by phosphorous-oxychloride (403 mg, 1.3 eq). The reaction was heated to 90° C. overnight, then cooled to room temperature and washed with ice cold water, then cold 0.5 M HCl, then cold sodium bicarbonate, then cold water, then brine, and then it was dried over sodium sulfate, and filtered through a plug of silica gel (eluting with 1:1 hexanes:EtOAc), and concentrated, and held under vacuum for 24 h. Crude product was a viscous purple oil. 1H-NMR (300 MHz, CDCl3) δ 7.70 (d, 1H), 7.40 (dd, 1H), 7.30-7.22 (m, 2H), 7.20-7.07 (m, 2H), 7.00 (d, 2H), 6.81-6.70 (m, 3H), 5.28 (d, 1H), 4.82 (d, 1H), 3.75 (s, 3H), 3.55 (t, 1H), 2.95 (s, 2H), 2.90-2.79 (m, 2H), 2.55-2.45 (m, 2H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with ice cold water
  3. dry with materialcold 0.5 M HCl, then cold sodium bicarbonate, then cold water, then brine, and then it was dried over sodium sulfate
  4. filtrationfiltered through a plug of silica gel (eluting with 1:1 hexanes:EtOAc)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-bf356d01fc43480e864bcadcb4e313d4
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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