Acetonitrile → (R)-3-[[N-(2-amino-5-(trifluoromethoxy)benzoyl]glycyl]amino]-1-(2,4-dichlorobenzyl)pyrrolidine

HRID 2187777Notes

Reaction equation

HRID 2187777 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]=[C:32]([Cl:34])[CH:31]=[CH:30][C:27]=1[CH2:28]Cl.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]([CH2:28][C:27]2[CH:30]=[CH:31][C:32]([Cl:34])=[CH:33][C:26]=2[Cl:25])[CH2:12]1)=[O:9])=[O:5]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 72122,4-Dichlorobenzyl chlorideHCID 11313986(R)-3-[2-(2-amino-5-trifluoromethoxybenzamido)acetamido]pyrrolidine

Product 1

HCID 54361675(R)-3-[[N-(2-amino-5-(trifluoromethoxy)benzoyl]glycyl]amino]-1-(2,4-dichlorobenzyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (R)-3-[{N-(2-amino-5-(trifluoromethoxy)benzoyl)glycyl}amino]pyrrolidine (0.050 mmol), 2,4-dichlorobenzyl chloride (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 (R)-3-[{N-(2-amino-5-(trifluoromethoxy)benzoyl)glycyl}amino]-1-(2,4-dichlorobenzyl)pyrrolidine (Compound No. 1905) (17.6 mg, 70%): The purity was determined by RPLC/MS (93%); ESI/MS m/e 505 (M++H, C21H21Cl2F3N4O3).

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-2180b2a625424b2ea6a41e019e36ffdb
Source dataset
uspto-grants-2002_06
Patent number
US06410566B1

Reaction notes

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