反应详情

In a 10 mL round-bottomed flask, (R)-2-cyclopropyl-N-(3,3-dimethyl-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.19 g, 0.34 mmol) was dissolved in dichloromethane (1.4 mL). Trifluoroacetic acid (1.05 mL, 13.7 mmol) was added and the light yellow reaction mixture was stirred at room temperature for 2 h then concentrated under reduced pressure. The residue was dissolved in toluene (3 mL), concentrated and then placed under high vacuum for 30 min. The resultant foam was dissolved in dichloromethane (1.4 mL) and ethylenediamine (1.40 mL, 20.7 mmol) was added. The light yellow reaction mixture was stirred at room temperature for 2 h then quenched with water and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over 8 g SiO2 with MeOH/CH2Cl2 (gradient: 0-10% MeOH) to afford a yellow solid. Trituration with EtOAc provided 63 mg (50%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide as a white powder. MS: (M+H)+=370; mp=201.0-203.0.

1. concentrationthen concentrated under reduced pressure
2. dissolutionThe residue was dissolved in toluene (3 mL)
3. concentrationconcentrated
4. waitplaced under high vacuum for 30 min
5. dissolutionThe resultant foam was dissolved in dichloromethane (1.4 mL)
6. stirringThe light yellow reaction mixture was stirred at room temperature for 2 h
7. customthen quenched with water
8. extractionextracted with EtOAc (2×50 mL)
9. washThe combined organic layers were washed with water and brine
10. dry with materialthen dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified by chromatography over 8 g SiO2 with MeOH/CH2Cl2 (gradient: 0-10% MeOH)
14. customto afford a yellow solid