Phenyl isocyanate → N-({[1-(4-Chloro-benzyl)-piperidin-4-ylmethyl]-carbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 279349Notes

Reaction equation

HRID 279349 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][CH:22]=1)[C:6]([NH:8][CH2:9][C:10]([NH:12][CH2:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:11])=[O:7].C1CCNCC1.[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Cl)=[CH:34][CH:33]=1.C1(N=C=O)C=CC=CC=1>CC#N>[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][N:17]2[CH2:18][CH2:19][CH:14]([CH2:13][NH:12][C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[C:5]3[CH:20]=[CH:21][CH:22]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:4]=3)[CH2:15][CH2:16]2)=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 7672Phenyl isocyanateHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 8082PiperidineHCID 184261644-[{N-(3(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine

Product 1

HCID 508750N-({[1-(4-Chloro-benzyl)-piperidin-4-ylmethyl]-carbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (30 mg, 0.087 mmol) in CH3CN (1.0 mL) and (piperidinomethyl)polystyrene (80 mg, 2.7 mmol base/g resin) were added to a solution of 4-chlorobenzyl chloride (11.7 mg, 0.073 mmol) in CH3CN (1.0 mL). The reaction mixture was stirred at 60° C. for 2 h. Phenyl isocyanate (10.4 mg, 0.087 mmol) was added to the cooled reaction mixture and the mixture was stirred at 25° C. for 1 h. The reaction mixture was loaded onto Varian™ SCX column and washed with CH3OH (20 mL). Product was eluted off using 2 N NH3 in CH3OH (6 mL) and concentrated to afford 1-(4-chlorobenzyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine as a colorless oil used without purification. Iodomethane (28 mg, 0.20 mmol) was added to a solution of 1-(4-chlorobenzyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine in CH3CN (2.0 mL) and the reaction mixture was stirred at 70° C. for 4 h. The solvent was removed under reduced pressure to afford 1-(4-chlorobenzyl)-1-methyl-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidinium iodide as a pale yellow oil (31.7 mg, 71%): The purity was determined by RPLC/MS (99%;); ESI/MS m/e 482.1 (M+, C24H28ClF3N3O2).

Workup

  1. stirringthe mixture was stirred at 25° C. for 1 h
  2. washwashed with CH3OH (20 mL)
  3. washProduct was eluted off
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4d1b84e05cd64119a9008154427c6f94
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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