Acetonitrile → (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine

HRID 1280959Notes

Reaction equation

HRID 1280959 reaction equation
[NH2:1][C:2]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)=[O:9])=[O:5].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Cl)=[C:28]([N+:34]([O-])=O)[CH:27]=1.C(#N)C>C(Cl)(Cl)Cl>[NH2:1][C:2]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:22])[F:23])=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][C@@H:11]1[CH2:15][CH2:14][N:13]([CH2:30][C:29]2[CH:32]=[CH:33][C:26]([Cl:25])=[CH:27][C:28]=2[NH2:34])[CH2:12]1)=[O:9])=[O:5]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 5983994-Chloro-1-(chloromethyl)-2-nitrobenzeneHCID 11313986(R)-3-[2-(2-amino-5-trifluoromethoxybenzamido)acetamido]pyrrolidine

Product 1

HCID 69212491(R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (R)-3-[{N-(2-amino-5-trifluoromethoxybenzoyl)glycyl}amino]pyrrolidine (0.050 mmol), 4-chloro-2-nitrobenzyl chloride (0.050 mmol), peperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.7 mL) was stirred overnight at 50° C. 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 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 (R)-3-[{N-(2-amino-5-trifluoromethoxybenzoyl)glycyl}amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine (Compound No. 1921) (2.2 mg, 6%): The purity was determined by RPLC/MS (81%); ESI/MS m/e 486.2 (M++H, C21H23ClF3N5O3).

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-1460683fabc44989a68192e8dc510880
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Reaction notes

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