4-Methoxycarbonylphenyl isothiocyanate → methyl 4-[(6-{[bis(3-methylbutyl)amino]carbonyl}-1-{3-[(tert-butoxycarbonyl) amino]propyl}-1H-benzimidazol-2-yl)amino]benzoate

HRID 1784256Notes

Reaction equation

HRID 1784256 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]=[C:12]=S)=[CH:7][CH:6]=1)=[O:4].[C:14]([O:18][C:19](=[O:45])[NH:20][CH2:21][CH2:22][CH2:23][NH:24][C:25]1[CH:30]=[C:29]([C:31]([N:33]([CH2:39][CH2:40][CH:41]([CH3:43])[CH3:42])[CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])=[O:32])[CH:28]=[CH:27][C:26]=1[NH2:44])([CH3:17])([CH3:16])[CH3:15]>O1CCCC1>[CH3:42][CH:41]([CH3:43])[CH2:40][CH2:39][N:33]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:31]([C:29]1[CH:28]=[CH:27][C:26]2[N:44]=[C:12]([NH:11][C:8]3[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)[N:24]([CH2:23][CH2:22][CH2:21][NH:20][C:19]([O:18][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:45])[C:25]=2[CH:30]=1)=[O:32]

Participants

4

Reactant 2

HCID 1380024-Methoxycarbonylphenyl isothiocyanateHCID 68792100Tert-butyl 3-[(2-amino-5-{[bis(3-methylbutyl)amino]carbonyl}phenyl)amino]propylcarbamate

Product 1

HCID 68792031methyl 4-[(6-{[bis(3-methylbutyl)amino]carbonyl}-1-{3-[(tert-butoxycarbonyl) amino]propyl}-1H-benzimidazol-2-yl)amino]benzoateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-methoxycarbonylphenyl isothiocyanate (327 mg, 1.5 eq) and N-methylcyclohexylcarbodiimide-N-methyl-polystyrene resin (acquired from Novabiochem; charge 1.9 mmol/g; 1.75 g, 3 eq) are added successively to a solution of tert-butyl-3-[(2-amino-5-{[bis(3-methylbutyl)amino]carbonyl}phenyl)amino]propylcarbamate (500 mg, 1 eq) in tetrahydrofuran (30 ml). The mixture is heated under reflux for 17 hours then cooled down to ambient temperature and aminomethylpolystyrene resin (acquired from Novabiochem, 2 eq) is added. After stirring for 4 hours at ambient temperature, the mixture is filtered on frit and the filtrate is concentrated under reduced pressure at 40° C. Purification of the residue by flash chromatography on silica gel (eluent: heptane/ethyl acetate 1:1) produces the expected compound in the form of a white solid (409 mg; 60% yield).

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 17 hours
  3. additionaminomethylpolystyrene resin (acquired from Novabiochem, 2 eq) is added
  4. filtrationthe mixture is filtered on frit
  5. concentrationthe filtrate is concentrated under reduced pressure at 40° C
  6. customPurification of the residue by flash chromatography on silica gel (eluent: heptane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-fc8de8111f194d8c9532cad28e293438
Source dataset
uspto-grants-2009_03
Patent number
US07501524B2

Reaction notes

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