Benzene, 1-isothiocyanato-4-nitro- → Tert-butyl 3-{6-{[bis(3-methylbutyl)amino]carbonyl}-2-[(4-nitrophenyl)amino]-1H-benzimidazol-1-yl}propylcarbamate

HRID 1161010Notes

Reaction equation

HRID 1161010 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]=[C:11]=S)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:13]([O:17][C:18](=[O:44])[NH:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]1[CH:29]=[C:28]([C:30]([N:32]([CH2:38][CH2:39][CH:40]([CH3:42])[CH3:41])[CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36])=[O:31])[CH:27]=[CH:26][C:25]=1[NH2:43])([CH3:16])([CH3:15])[CH3:14]>O1CCCC1>[CH3:41][CH:40]([CH3:42])[CH2:39][CH2:38][N:32]([CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36])[C:30]([C:28]1[CH:27]=[CH:26][C:25]2[N:43]=[C:11]([NH:10][C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[N:23]([CH2:22][CH2:21][CH2:20][NH:19][C:18](=[O:44])[O:17][C:13]([CH3:16])([CH3:14])[CH3:15])[C:24]=2[CH:29]=1)=[O:31]

Participants

4

Reactant 2

HCID 75044Benzene, 1-isothiocyanato-4-nitro-HCID 68792100Tert-butyl 3-[(2-amino-5-{[bis(3-methylbutyl)amino]carbonyl}phenyl)amino]propylcarbamate

Product 1

HCID 68794987Tert-butyl 3-{6-{[bis(3-methylbutyl)amino]carbonyl}-2-[(4-nitrophenyl)amino]-1H-benzimidazol-1-yl}propylcarbamateYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-nitrophenyl isothiocyanate (305 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 successively added to a solution of tert-butyl-3-[(2-amino-5-{[bis(3-methylbutyl)amino]carbonyl}phenyl)amino]propylcarbamate prepared according to Example A1 (500 mg, 1 eq) in tetrahydrofuran (30 ml). The mixture is heated under reflux for 18 hours then cooled down to ambient temperature and filtered on frit. The filtrate is concentrated under reduced pressure at 40° C. Purification of the residue by flash chromatography on silica gel (eluent: heptane/ethyl acetate 7:3 to 2:8) produces the expected compound in the form of a yellow solid (584 mg; 88% yield).

Workup

  1. customprepared
  2. temperatureThe mixture is heated
  3. temperatureunder reflux for 18 hours
  4. filtrationfiltered 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 7:3 to 2:8)

Sources & evidence

ORD record
ord-18330047ace744d99469c55a3134956d
Source dataset
uspto-grants-2010_10
Patent number
US07816539B2

Reaction notes

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