反应详情

A mixture of (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]pyrrolidine (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. The resulting reaction mixture was cooled, loaded onto a Varian™ SCX column and washed with 50% chloroform/methanol (10 mL) and methanol (10 mL). The obtained crude product was eluted with a solution of 2 M NH3 in methanol (5 mL) and concentrated. Ethanol (3 mL) and 10% palladium carbon were added to the resulting residue, and the solution was stirred at room temperature under a hydrogen atmosphere for 1.5 hours. The obtained solution was filtered, concentrated and then purified by preparative TLC to thereby provide (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine (Compd. No. 1921) (2.2 mg, 6%). The purity was determined by RPLC/MS (81%). ESI/MS m/e 486.2 (M++H, C21H23ClF3N5O3).

1. customovernight
2. customThe resulting reaction mixture
3. temperaturewas cooled
4. washwashed with 50% chloroform/methanol (10 mL) and methanol (10 mL)
5. customThe obtained crude product
6. washwas eluted with a solution of 2 M NH3 in methanol (5 mL)
7. concentrationconcentrated
8. additionEthanol (3 mL) and 10% palladium carbon were added to the resulting residue
9. filtrationThe obtained solution was filtered
10. concentrationconcentrated
11. custompurified by preparative TLC to thereby provide (R)-3-[[N-(2-amino-5-trifluoromethoxybenzoyl)glycyl]amino]-1-(2-amino-4-chlorobenzyl)pyrrolidine (Compd. No