反应详情

In a round-bottomed flask, 2-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (62 mg, 0.091 mmol) was dissolved in dichloromethane (0.5 mL) and trifluoroacetic acid (0.28 mL) was added. The yellow reaction mixture was stirred at room temperature for 2.75 h then concentrated under reduced pressure. The residue was dissolved in dichloromethane (0.5 mL) and ethylenediamine (0.37 mL) was added. The reaction mixture was stirred at room temperature for 1.25 h then quenched with 5 mL water and extracted with EtOAc (2×). The combined organic layers were washed with 5 mL water and 5 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 8 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-4% MeOH). All fractions containing product were combined and concentrated to afford 28 mg (61%) of 2-(4-tert-butyl-pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a yellow foamy solid. MS: (M+H)+=486.

1. concentrationthen concentrated under reduced pressure
2. dissolutionThe residue was dissolved in dichloromethane (0.5 mL)
3. additionethylenediamine (0.37 mL) was added
4. stirringThe reaction mixture was stirred at room temperature for 1.25 h
5. customthen quenched with 5 mL water
6. extractionextracted with EtOAc (2×)
7. washThe combined organic layers were washed with 5 mL water and 5 mL brine
8. dry with materialthen dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was chromatographed over 8 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-4% MeOH)
12. additionAll fractions containing product
13. concentrationconcentrated