Triethylamine → 1-((4-((((3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl)amino)methyl)piperidin-1-yl)methyl)cyclobutanecarboxylic acid

HRID 645987Notes

Reaction equation

HRID 645987 reaction equation
[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]1=[O:13])([CH3:3])[CH3:2].[N+](C1C=C[C:20]([O:23]C(Cl)=O)=CC=1)([O-])=O.CCN(CC)CC.CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:45][CH2:46][CH:47]1[CH2:52][CH2:51][N:50]([CH2:53][C:54]2([C:58]([OH:60])=[O:59])[CH2:57][CH2:56][CH2:55]2)[CH2:49][CH2:48]1>C(Cl)Cl>[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:20]([NH:45][CH2:46][CH:47]2[CH2:52][CH2:51][N:50]([CH2:53][C:54]3([C:58]([OH:60])=[O:59])[CH2:57][CH2:56][CH2:55]3)[CH2:49][CH2:48]2)=[O:23])[C:5]1=[O:13])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 16535801-(Propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 866021201-{[4-(Aminomethyl)piperidin-1-yl)methyl]cyclobutanecarboxylic acid 4-methylbenzenesulfonate

Product 1

HCID 116618921-((4-((((3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl)amino)methyl)piperidin-1-yl)methyl)cyclobutanecarboxylic acidYield 216.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (486 mg, 2.8 mmol) and chloroformic acid 4-nitrophenyl ester (556 mg, 2.8 mmol) in CH2Cl2 (10 mL) was stirred at room temperature for 5 min. To this mixture, Et3N (0.84 mL, 6.1 mmol) was added slowly and this mixture became a solution. This solution was added to a mixture of 1-{[4-(aminomethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid 4-methylbenzene sulfonate (1.1 g, 2.8 mmol, Step 7) in CH2Cl2 (5 mL) at room temperature. After stirring for 10 min, Et3N (0.38 mL, 2.8 mmol) was added and the resulting mixture was stirred at room temperature for 2 hr. This mixture was washed with 0.5 N HCl aq (10 mL) and saturated NaHCO3 aq (10 mL) then the organic layer was concentrated. To the residue, saturated NaHCO3 aq (15 mL) and heptane (15 mL) was added at room temperature and it was stirred for 6 hrs at that temperature. Solid was observed and this mixture was filtered. The obtained solid was washed with H2O and heptane. After drying, crude material was obtained (1.0 g, 82%) as white solid. This crude material (4.0 g) was purified by recrystallization from toluene (36 mL) to give 2.6 g of the titled compound (66%) as white solid.

Workup

  1. stirringAfter stirring for 10 min
  2. stirringthe resulting mixture was stirred at room temperature for 2 hr
  3. washThis mixture was washed with 0.5 N HCl aq (10 mL) and saturated NaHCO3 aq (10 mL)
  4. concentrationthe organic layer was concentrated
  5. additionTo the residue, saturated NaHCO3 aq (15 mL) and heptane (15 mL) was added at room temperature
  6. stirringit was stirred for 6 hrs at that temperature
  7. filtrationthis mixture was filtered
  8. washThe obtained solid was washed with H2O and heptane
  9. customAfter drying
  10. customcrude material was obtained (1.0 g, 82%) as white solid
  11. customThis crude material (4.0 g) was purified by recrystallization from toluene (36 mL)

Sources & evidence

ORD record
ord-5fb863f883df45e7930df9bc40694872
Source dataset
uspto-grants-2010_04
Patent number
US07705020B2

Reaction notes

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