Potassium Hydroxide → 2-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole-6-carboxamide

HRID 50434Notes

Reaction equation

HRID 50434 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([CH2:11][CH3:12])[N:8]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][NH:21][C:22]([NH:24][S:25]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)(=[O:27])=[O:26])=[O:23])=[CH:15][CH:14]=3)[C:7]=2[CH:35]=1)#[N:2].[OH-:36].[K+]>CC(O)(C)C>[CH2:11]([C:9]1[N:8]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][NH:21][C:22]([NH:24][S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])=[O:23])=[CH:15][CH:14]=2)[C:7]2[CH:35]=[C:3]([C:1]([NH2:2])=[O:36])[CH:4]=[CH:5][C:6]=2[N:10]=1)[CH3:12]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 21875569HCID 21875569, compound

Product 1

HCID 218762972-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole-6-carboxamideYield 63%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a solution of 6-cyano-2-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole (Example 85, 162 mg, 0.33 mmol) in 2-methyl-2-propanol (10 mL) was added powdered KOH (66 mg, 1.0 mmol). The resulting mixture was heated at reflux temperature for 3 h. After removal of solvent, the reaction mixture was partitioned between dichloromethane (50 mL) and phosphate buffer (50 mL). The organic phase was separated and the aqueous phase was extracted with dichloromethane (50 mL). The combined organic phases were washed with brine (50 mL), dried (Na2SO4), and concentrated. The residual solids were recrystallized from ethyl acetate to afford 105 mg (63%) of the title compound as white solids: H-NMR (CDCl3) δ: 7.79 (2H, d, J=8.4 Hz), 7.75 (1H, d, J=8.8 Hz), 7.71-7.63 (2H, m), 7.35-7.25 (4H, m), 7.16 (2H, d, J=8.4 Hz), 6.75 (2H, br.s), 6.55 (1H, br.s), 3.54 (2H, t, J=6.4 Hz), 2.8 (2H, t, J=6.4 Hz), 2.79 (2H, q, J=7.5 Hz), 2.40 (3H, s), 1.34 (3H, t, J=7.5 Hz).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux temperature for 3 h
  3. customAfter removal of solvent
  4. customthe reaction mixture was partitioned between dichloromethane (50 mL) and phosphate buffer (50 mL)
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with dichloromethane (50 mL)
  7. washThe combined organic phases were washed with brine (50 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe residual solids were recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-06c8d1bcf31b44d2bb263f0f3e679598
Source dataset
uspto-grants-2004_03
Patent number
US06710054B2

Reaction notes

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