Aluminum(III) Chloride → (Z)-7-chloro-3-(2-chlorobenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 2263706Notes

Reaction equation

HRID 2263706 reaction equation
[Cl:1][C:2]1[CH:40]=[CH:39][C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:29])[CH:8]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])[N:9]=[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[NH:15][C:16](=[O:18])[NH:17][C:13]=4[CH:12]=3)[C:4]=2[CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-]>C1(OC)C=CC=CC=1>[Cl:1][C:2]1[CH:40]=[CH:39][C:5]2[NH:6][C:7](=[O:29])[CH:8]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:28])[N:9]=[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[NH:15][C:16](=[O:18])[NH:17][C:13]=4[CH:12]=3)[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 59594383(Z)-7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Product 1

HCID 25015236(Z)-7-chloro-3-(2-chlorobenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 44.3%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
85 °C

Procedure

(Z)-7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (200 mg, 0.35 mmol) was dissolved in anhydrous anisole (4 mL) under a nitrogen atmosphere, aluminum chloride (280 mg, 2.1 mmol) was added and the mixture was heated to 85° C. for 1 hour. The solution was cooled to ambient temperature, poured onto ice, rinsing the flask with ethyl acetate and water. The mixture was slurried for 10 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried with sodium sulfate, decanted and concentrated in the presence of silica gel. The residue was chromatographed on silica gel eluting with 70-100% ethyl acetate in hexanes switching to a gradient of 0-10% methanol in ethyl acetate to give (Z)-7-chloro-3-(2-chlorobenzyl)-5-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (70 mg, 44%). 1H NMR (300 MHz, DMSO-d6) δ 3.46 (d, 2H) 3.76 (t, 1H), 6.90 (m, 2H), 7.01 (s, 1H) 7.21-7.64 (m, 7H), 10.70 (s, 1H), 10.74 (s, 1H), 10.85 (s, 1H); ESI m/z measured 451.0736 [M+H+], calculated 451.0729.

Workup

  1. temperatureThe solution was cooled to ambient temperature
  2. additionpoured onto ice
  3. washrinsing the flask with ethyl acetate and water
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with sodium sulfate
  8. customdecanted
  9. concentrationconcentrated in the presence of silica gel
  10. customThe residue was chromatographed on silica gel eluting with 70-100% ethyl acetate in hexanes switching to a gradient of 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-60895eae16174916a66a9b8252928419
Source dataset
uspto-grants-2010_12
Patent number
US07851465B2

Reaction notes

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