反应详情

A mixture of (R)-3-[[N-(2-amino-5-(trifluoromethoxyl)benzoyl)glycyl]amino]pyrrolidine (0.050 mmol) with 2,4-dichlorobenzyl chloride (0.066 mL), a piperidinomethylpolystyrene (60 mg), acetonitrile (0.8 mL) and chloroform (0.5 mL) was stirred at 60° C. for 12 hours. The resulting reaction mixture was cooled to room temperature, loaded onto a Varian™ SCX column and washed with a 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. A 1,4-dioxane (2 mL) solution of 4 M HCl was added to the resulting residue, and the obtained mixture was stirred at room temperature overnight, concentrated and then purified by preparative TLC to afford (R)-3-[[N-(2-amino-5-(trifluoromethoxy)benzoyl]glycyl]amino]-1-(2,4-dichlorobenzyl)pyrrolidine (Compd. No. 1905) (17.6 mg, 70%). The purity was determined by RPLC/MS (93%). ESI/MS m/e 505 (M++H, C21H21Cl2F3N4O3).

1. customThe resulting reaction mixture
2. washwashed with a 50% chloroform/methanol (10 mL) and methanol (10 mL)
3. customThe obtained crude product
4. washwas eluted with a solution of 2 M NH3 in methanol (5 mL)
5. concentrationconcentrated
6. additionA 1,4-dioxane (2 mL) solution of 4 M HCl was added to the resulting residue
7. concentrationconcentrated
8. custompurified by preparative TLC