Methyl iodide → N-(3,5-Dichlorophenyl)-1-methyl-1H-benzimidazol-2-amine

HRID 230009

Reaction equation

HRID 230009 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:9])[CH:8]=1)[NH2:5].[CH3:10]CN(C(C)C)C(C)C.C(Cl)(Cl)=S.[CH3:23][NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH2:31].CI>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:23]2[N:31]([CH3:10])[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[N:24]=2)[CH:6]=[C:7]([Cl:9])[CH:8]=1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 10040ThiophosgeneHCID 122813,5-DichloroanilineHCID 78498N-Methyl-o-phenylenediamineHCID 81531Diisopropylethylamine2×

Product 1

HCID 923860N-(3,5-Dichlorophenyl)-1-methyl-1H-benzimidazol-2-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3,5-dichloroaniline (6.2 mmol, 1.0 g) and DIEA (6.8 mmol, 1.2 mL) in 10 mL of DCM was slowly added thiophosgene (6.2 mmol, 472 μL) (exothermic). After 30 min, N-methyl-1,2-phenylenediamine (6.2 mmol, 704 μL) was added and the reaction mixture was allowed to stand at ambient temperature for 1 h. MeI (6.2 mmol, 386 μL), followed by DIEA (6.8 mmol, 1.2 mL) were then added, and the reaction mixture was allowed to stand at ambient temperature overnight. The crude reaction was partitioned between DCM/brine. The organic layer was collected and the aqueous phase was extracted twice with DCM. The combined organic layer was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica eluting with 2% MeOH/DCM and 4% MeOH/DCM, affording the product as a tan solid. 1H NMR (500 MHz, d6-DMSO) δ 9.35 (s, 1H), 8.04 (s, 2H), 7.48 (m, 2H), 7.36 (m, 2H), 7.08-7.14 (overlapping m, 2H), 3.73 (s, 3H). MS (ESI): m/z 292 (M+H). HPLC A: 1.38 min.

Workup

  1. waitto stand at ambient temperature for 1 h
  2. additionwere then added
  3. waitto stand at ambient temperature overnight
  4. customThe crude reaction
  5. customwas partitioned between DCM/brine
  6. customThe organic layer was collected
  7. extractionthe aqueous phase was extracted twice with DCM
  8. concentrationThe combined organic layer was concentrated under reduced pressure
  9. customthe residue was purified by flash chromatography on silica eluting with 2% MeOH/DCM and 4% MeOH/DCM

Sources & evidence

ORD record
ord-e54b6b714df3423692ea35c85445ccb2
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Linked notes

Loading…