反应详情

In a round-bottomed flask were combined 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (180 mg, 0.54 mmol), 3-amino-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (214 mg, 0.87 mmol), EDC (114 mg, 0.59 mmol), and HOBt (80 mg, 0.59 mmol). Then added DMF (2.4 mL) followed by i-Pr2NEt (0.14 mL, 0.80 mmol). The reaction mixture was stirred at room temperature overnight then quenched with H2O and extracted with Et2O (2×). The combined organics were washed with H2O (2×) and brine then dried over Na2SO4 and concentrated. The residue was purified by chromatography over 24 g of SiO2 using EtOAc/hexanes (gradient: 0-40% EtOAc) to afford 276 mg (91%) of 3-{[2-Cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester as an off-white foam.

1. customIn a round-bottomed flask were combined
2. customthen quenched with H2O
3. extractionextracted with Et2O (2×)
4. washThe combined organics were washed with H2O (2×) and brine
5. dry with materialthen dried over Na2SO4
6. concentrationconcentrated
7. customThe residue was purified by chromatography over 24 g of SiO2