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

HRID 133619Notes

Reaction equation

HRID 133619 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

Procedure

A mixture of 4-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]aminomethyl]piperidine (0.050 mmol) with 4-chloro-2-nitrobenzyl chloride (0.050 mmol), a piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.7 mL) was stirred at 50° C. overnight, cooled, then loaded onto a Varian™ SCX column and washed with chloroform/methanol (10 mL) and methanol (10 mL). The obtained product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. Ethanol (3 mL) and a 10% palladium carbon (15 mg) were added to the resulting residue, and the obtained mixture was stirred at room temperature under a hydrogen atmosphere for 1.5 hours and filtered. The filtrate was concentrated and then purified by preparative TLC to thereby afford 4-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]aminomethyl]-1-(2-amino-4-chlorobenzyl)piperidine (Compd. No. 1919) (5.1 mg, 14%). The purity was determined by RPLC/MS (90%). 1H NMR (400 MHz, CDCl3) δ 1.09-1.32 (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, H), 3.17 (t. J=6.5 Hz, 2H), 3.42 (s, 2H), 4.05 (d, J=3.5 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, C23H27ClF3N5O2).

Workup

  1. temperaturecooled
  2. washwashed with chloroform/methanol (10 mL) and methanol (10 mL)
  3. washThe obtained product was eluted with a 2 M methanol solution of NH3 (5 mL)
  4. concentrationconcentrated
  5. additionEthanol (3 mL) and a 10% palladium carbon (15 mg) were added to the resulting residue
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. custompurified by preparative TLC to thereby afford 4-[[N-(2-amino-5-trifluoromethylbenzoyl)glycyl]aminomethyl]-1-(2-amino-4-chlorobenzyl)piperidine (Compd. No

Sources & evidence

ORD record
ord-5d0032a2a7cc4dad9552b8812cb1c326
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

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