Acetic Acid → Methyl (3-methyl-5-(4-aminophenoxy)-benzimidazol-2-yl)carbamate

HRID 1294063Notes

Reaction equation

HRID 1294063 reaction equation
[CH3:1][NH:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][C:16]=1[N+:17]([O-])=O)[O:6][C:7]1[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=1.[CH3:20][O:21][C:22]([NH:24][C:25](=NC(OC)=O)SC)=[O:23].CC(O)=O>CO.[Pd]>[CH3:1][N:2]1[C:3]2[CH:4]=[C:5]([O:6][C:7]3[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=3)[CH:14]=[CH:15][C:16]=2[N:17]=[C:25]1[NH:24][C:22](=[O:23])[O:21][CH3:20]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 177559824-(3-Methylamino-4-nitrophenoxy)aniline2×

Product 1

HCID 17755983Methyl (3-methyl-5-(4-aminophenoxy)-benzimidazol-2-yl)carbamateYield 85%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
85 °C

Procedure

After hydrogenation of 4-(3-methylamino-4-nitrophenoxy)aniline (Intermediate 8G-519.2 mg, 2.0 mmol) with 5% Pd—C in MeOH (20 mL), 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (1.03 g, 5.0 mmol) and AcOH (2.0 mL) was added then stirred at 85° C. for 5.5 hrs. After cooling, the mixture was added 2N HClaq. (25 mL) then stirred at 65° C. for 2 hrs. The mixture was passed through celite pad to remove catalyst and the solvent was removed by evaporation. The residue was extracted with ethyl acetate. The organic layer was washed with NH4OH(aq). and brine, dried over Na2SO4 then evaporated. Sequence purification on SiO2 column chromatography gave the title compound (529.1 mg, 85%): MS m/e 313 (M+1).

Workup

  1. temperatureAfter cooling
  2. additionthe mixture was added 2N HClaq
  3. stirring(25 mL) then stirred at 65° C. for 2 hrs
  4. customto remove catalyst
  5. customthe solvent was removed by evaporation
  6. extractionThe residue was extracted with ethyl acetate
  7. washThe organic layer was washed with NH4OH(aq)
  8. dry with materialand brine, dried over Na2SO4
  9. customthen evaporated
  10. customSequence purification on SiO2 column chromatography

Sources & evidence

ORD record
ord-2d50fc364c034066bba52de72684b015
Source dataset
uspto-grants-2007_07
Patent number
US07238813B2

Reaction notes

Loading…