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

A mixture of (R)-3-[{N-(2-amino-5-(trifluoromethoxy)benzoyl)glycyl}amino]pyrrolidine (0.050 mmol), 2,4-dichlorobenzyl chloride (0.060 mmol), peperidinomethylpolystyrene (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).

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

ORDレコード

ord-c279a4b88e2f4ac197ae1e9dd94d6df2

出典データセット

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06451842B1