Ethyl Acetate → 7-chloro-3-(2-chlorobenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 1186076Notes

Reaction equation

HRID 1186076 reaction equation
[Cl:1][C:2]1[CH:41]=[CH:40][C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:30])[CH:8]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:21]=[CH:20][C:14]4[NH:15][C:16](=[O:19])[N:17]([CH3:18])[C:13]=4[CH:12]=3)[C:4]=2[CH:3]=1.[Al+3].[Cl-].[Cl-].[Cl-].C(OCC)(=O)C>C1(OC)C=CC=CC=1.ClC(Cl)=C>[Cl:1][C:2]1[CH:41]=[CH:40][C:5]2[NH:6][C:7](=[O:30])[CH:8]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])[N:9]=[C:10]([C:11]3[CH:21]=[CH:20][C:14]4[NH:15][C:16](=[O:19])[N:17]([CH3:18])[C:13]=4[CH:12]=3)[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 8857Ethyl Acetate2×HCID 6451240Aluminum(III) ChlorideHCID 670608427-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Product 1

HCID 670608337-chloro-3-(2-chlorobenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 59%

Reagents, catalysts & solvents 2

HCID 6366Vinylidene chlorideSolventHCID 7519AnisoleSolvent

Conditions

Temperature
85 °C

Procedure

7-Chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.4 g, 0.68 mmol) was dissolved in 10% anisole in 1,1-dichloroethene (DCE, 3 mL) under nitrogen and AlCl3 (0.455 g, 3.42 mmol) was added in one portion. The resulting orange solution was heated to 85° C. for 1.5 h. The solution was allowed to cool. Ethyl acetate was added followed by ice water. This mixture was stirred for 30 min (turned from yellow to colorless) then partitioned and the organic layer was washed with water then brine. The organic layer was dried over MgSO4, then filtered to give a clear, very pale yellow solution. Silica gel was added and the solvent was removed under reduced pressure. Chromatography on silica gel eluting with 5-50-100% ethyl acetate in hexanes gave 7-chloro-3-(2-chlorobenzyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one as a white solid (59% yield).

Workup

  1. temperatureto cool
  2. customthen partitioned
  3. washthe organic layer was washed with water
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customto give a clear, very pale yellow solution
  7. additionSilica gel was added
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-dd31e56271eb4a9abfe79a4d1921f3b8
Source dataset
uspto-grants-2014_03
Patent number
US08673897B2

Reaction notes

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