Acetonitrile → 4-[{N-(2-amino-5-trifluoromethoxybenzoyl) glycyl}aminomethyl]-1-(4-bromobenzyl)piperidine

HRID 279338Notes

Reaction equation

HRID 279338 reaction equation
C(OC([NH:8][C:9]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:16])=[O:12])=O)(C)(C)C.[Br:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Br)=[CH:37][CH:36]=1.C(#N)C>C(Cl)(Cl)Cl>[NH2:8][C:9]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:39][C:38]2[CH:41]=[CH:42][C:35]([Br:34])=[CH:36][CH:37]=2)[CH2:21][CH2:20]1)=[O:16])=[O:12]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 685274-Bromobenzyl bromideHCID 184262354-[{N-(2-(tert-butoxycarbonylamino)-5-trifluoromethoxybenzoyl)glycyl}aminomethyl]piperidine

Product 1

HCID 184262314-[{N-(2-amino-5-trifluoromethoxybenzoyl) glycyl}aminomethyl]-1-(4-bromobenzyl)piperidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-5-trifluoromethoxybenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 4-bromobenzyl bromide (0.060 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (0.8 mL) and chloroform (0.5 mL) was stirred at 60° C. for 12 h. The reaction mixture was cooled, loaded onto Varian™ SCX column and washed with 50% CHCl3/CH3OH (10 mL) and CH3OH (10 mL). Product was eluted using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material was added 4 N HCl in 1,4-dioxane (2 mL), and the solution was stirred overnight at room temperature. Concentration and preparative TLC afforded 4-[{N-(2-amino-5-trifluoromethoxybenzoyl)glycyl}aminomethyl]-1-(4-bromobenzyl)piperidine (Compound No. 1910) (6.5 mg, 24%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 545 (M++H, C23H26BrF3N4O3).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with 50% CHCl3/CH3OH (10 mL) and CH3OH (10 mL)
  3. washProduct was eluted
  4. concentrationconcentrated
  5. additionTo the resulting material was added 4 N HCl in 1,4-dioxane (2 mL)
  6. stirringthe solution was stirred overnight at room temperature
  7. concentrationConcentration and preparative TLC

Sources & evidence

ORD record
ord-1be7cfb436504a7cb43a0b3d56bc0cc4
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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