Acetonitrile → 4-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]aminomethyl]-1-(2-amino-4-chlorobenzyl)piperidine

HRID 279339Notes

Reaction equation

HRID 279339 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:9])=[O:5].[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Cl)=[C:29]([N+:35]([O-])=O)[CH:28]=1.C(#N)C>C(Cl)(Cl)Cl>[NH2:1][C:2]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:23])[F:24])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][CH2:11][CH:12]1[CH2:13][CH2:14][N:15]([CH2:31][C:30]2[CH:33]=[CH:34][C:27]([Cl:26])=[CH:28][C:29]=2[NH2:35])[CH2:16][CH2:17]1)=[O:9])=[O:5]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 5983994-Chloro-1-(chloromethyl)-2-nitrobenzeneHCID 184262274-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]aminomethyl]piperidine

Product 1

HCID 98704904-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]aminomethyl]-1-(2-amino-4-chlorobenzyl)piperidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-[{N-(2-amino-5-trifluoromethylbenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 4-chloro-2-nitrobenzyl chloride (0.050 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.7 mL) was stirred overnight at 50° C. The reaction mixture was cooled, loaded onto Variant™ 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 ethanol (3 mL) and 10% Pd—C (15 mg), and the mixture was stirred under H2 at room temperature for 1.5 h. Filtration, concentration, and preparative TLC afforded 4-[{N-(2-amino-5-trifluoromethylbenzoyl)glycyl}aminomethyl]-1-(2-amino-4-chlorobenzyl)piperidine (Compound No. 1919) (5.1 mg, 14%): The purity was determined by RPLC/MS (90%); 1H NMR (400 MHz, CDCl3) δ1.09-1.32 (m, 4H), 1.41-1.59 (m, 1H), 1.66 (d, J=12.5 Hz, 2H), 1.88 (t, J=11.5 Hz, 2H), 2.82 (d, J=11.5 Hz, 2H), 3.17 (t, J=6.5 Hz, 2H), 3.42 (s, 2H), 4.05 (d, J=5.5 Hz, 2H), 4.85 (br s, 1H), 5.92 (br s, 2H), 6.25-6.36 (m, 1H), 6.55-6.66 (m, 1H), 6.70 (d, J=8.5 Hz, 1H), 6.85 (d, J=8.5 Hz, 1H), 7.26 (s, 1H), 7.42 (d, J=8.5 Hz, 1H), 7.68 (s, 1H); ESI/MS m/e 498.2 (M++H, C23H27ClF3N5O3).

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 ethanol (3 mL) and 10% Pd—C (15 mg)
  6. stirringthe mixture was stirred under H2 at room temperature for 1.5 h
  7. filtrationFiltration, concentration, and preparative TLC

Sources & evidence

ORD record
ord-4023b67f7d3d454c8834d67a1dccd062
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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