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

HRID 724078Notes

Reaction equation

HRID 724078 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: 1H-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), 2.88 (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-4aa5e1b1f1b74b18ab651ad5c040ae84
Source dataset
uspto-grants-2006_11
Patent number
US07141580B2

Reaction notes

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