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

HRID 1186063Notes

Reaction equation

HRID 1186063 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]2[N:6]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:7](=[O:20])[CH:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[NH:9][C:10](=O)[C:4]=2[CH:3]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:43])=O>C1(C)C=CC=CC=1>[Cl:43][C:10]1[C:4]2[CH:3]=[C:2]([Cl:1])[CH:31]=[CH:30][C:5]=2[N:6]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=2)[C:7](=[O:20])[CH:8]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[N:9]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 595943957-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Product 1

HCID 595943935,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 100.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (0.65 g, 1.43 mmol) was suspended in anhydrous toluene (10 mL) under a nitrogen atmosphere. N,N-Dimethylaniline (0.36 mL, 2.9 mmol) was added followed by phosphorus oxychloride (0.20 mL, 2.1 mmol) and the mixture was heated at 90° C. for 4 hours. After cooling to ambient temperature, the mixture was diluted with 40 mL of ethyl acetate:hexanes (1:2), washed with ice water (10 mL), ice cold 1 M hydrogen chloride (2×10 mL), and brine, then dried with sodium sulfate, decanted and concentrated in vacuo. The residue was redissolved in a small amount of ethyl acetate, then poured onto a silica plug. The product was eluted with 100 mL of ethyl acetate:hexanes (1:2) to yield (E)-5,7-dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (680 mg, 100%) which was used without further purification.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. washwashed with ice water (10 mL), ice cold 1 M hydrogen chloride (2×10 mL), and brine
  3. dry with materialdried with sodium sulfate
  4. customdecanted
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was redissolved in a small amount of ethyl acetate
  7. additionpoured onto a silica plug
  8. washThe product was eluted with 100 mL of ethyl acetate:hexanes (1:2)

Sources & evidence

ORD record
ord-867b864f28c94ebeaaa1740b0de2c1c9
Source dataset
uspto-grants-2014_03
Patent number
US08673897B2

Reaction notes

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