Hydrochloric Acid → 1-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acid

HRID 736415

Reaction equation

HRID 736415 reaction equation
[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([CH2:23][C:24]3([C:29]([O:31]C)=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH2:19][CH2:18]2)=[O:14])[C:5]1=[O:33])([CH3:3])[CH3:2].Cl>C(O)(=O)C>[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]([NH:15][CH2:16][CH:17]2[CH2:18][CH2:19][N:20]([CH2:23][C:24]3([C:29]([OH:31])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH2:21][CH2:22]2)=[O:14])[C:5]1=[O:33])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68584479Methyl 1-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylate

Product 1

HCID 115105321-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acidYield 87.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of Methyl 1-{[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylate (1.33 g, 2.90 mmol, Step 4) in 4N—HCl (6 mL) and acetic acid (6 mL) was stirred at reflux for 18 h. After cooling, the reaction mixture was concentrated and basified with sat. NaHCO3 aq. (100 mL), extracted with CH2Cl2 (150 mL) for three times. The combined extracts were dried over Na2SO4, filtered and concentrated. The residue was chromatographed on a column of silica gel eluted with MeOH/CH2Cl2 (1:10) to give 1.12 g (85%) of title compound as white solid. The crude compound was recrystallized from EtOAc×2 and dried in vacuo at 50° C. for 2 days to give 610 mg of title compound as white crystal.

Workup

  1. temperatureat reflux for 18 h
  2. temperatureAfter cooling
  3. concentrationthe reaction mixture was concentrated
  4. extractionextracted with CH2Cl2 (150 mL) for three times
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on a column of silica gel
  9. washeluted with MeOH/CH2Cl2 (1:10)

Sources & evidence

ORD record
ord-06f9a31364ea4bafb79edbc7559d6fdf
Source dataset
uspto-grants-2009_09
Patent number
US07595329B2

Linked notes

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