Hydrochloric Acid → 6-Chloro-2-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole-5-carboxylic acid

HRID 858466Notes

Reaction equation

HRID 858466 reaction equation
[Cl:1][C:2]1[C:3]([C:35](N)=[O:36])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH3:11])[N:7]([C:12]3[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][NH:20][C:21]([NH:23][S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])=[O:22])=[CH:14][CH:13]=3)[C:6]=2[CH:34]=1.[OH-:38].[K+].O.Cl>CO>[Cl:1][C:2]1[C:3]([C:35]([OH:36])=[O:38])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH3:11])[N:7]([C:12]3[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][NH:20][C:21]([NH:23][S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:25])=[O:26])=[O:22])=[CH:16][CH:17]=3)[C:6]=2[CH:34]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14797Potassium HydroxideHCID 218759866-Chloro-2-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1h-benzimidazole-5-carboxamide

Product 1

HCID 213004486-Chloro-2-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole-5-carboxylic acidYield 25.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-2-ethyl-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole-5-carboxamide (Example 111, 140 mg, 0.26 mmol) and KOH (63 mg, 0.8 mmol) in methanol (10 mL) was stirred at 100° C. for 1 day. The mixture was poured into water, acidified with 2N hydrochloric acid, and extracted with ethyl acetate (50 mL). The organic layer was washed with brine (30 mL), dried (Na2SO4), and concentrated. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane/methanol (10:1) to afford 36 mg (25%) of the title compound as white solids: mp 145–150° C.; MS (ESI) m/z 541 (M+H)+; 1H-NMR (DMSO-d6) δ 8.10 (1H, s), 7.76 (2H, d, J=7.9 Hz), 7.36–7.47 (6H, m), 7.10 (1H, s), 3.28 (2H, m), 2.69–2.81 (4H, m), 2.34 (3H, s), 1.24 (3H, t, J=7.5 Hz); IR (KBr) νmax: 3450, 1701, 1517, 1340, 1163, 1091, 900 cm−1.

Workup

  1. extractionextracted with ethyl acetate (50 mL)
  2. washThe organic layer was washed with brine (30 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane/methanol (10:1)

Sources & evidence

ORD record
ord-9e666bc1a01b4b1299d256fb0cd8a352
Source dataset
uspto-grants-2006_12
Patent number
US07148234B2

Reaction notes

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