反应详情

A solution of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (0.104 g, 0.195 mmol, contains some 2-chloro impurity), 1 mL of dichloromethane and 1 mL of TFA was stirred for 3 h, then concentrated to a pale yellow oil. The oil was dissolved in 0.5 mL of dichloromethane and 0.5 mL of ethylene diamine, and the yellow solution was stirred for 1.25 h, then partitioned between 5 mL of water and 10 mL of ethyl acetate. The aqueous layer was extracted with 10 mL of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated to give 0.087 g of 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a pale yellow residue, which was used without further purification. MS: (M+Na)+=427. A major impurity is 2-chloro-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide. MS: (M+Na)+=381. Approximate 3:1 ratio of Br:Cl.

1. concentrationconcentrated to a pale yellow oil
2. dissolutionThe oil was dissolved in 0.5 mL of dichloromethane
3. stirring0.5 mL of ethylene diamine, and the yellow solution was stirred for 1.25 h
4. custompartitioned between 5 mL of water and 10 mL of ethyl acetate
5. extractionThe aqueous layer was extracted with 10 mL of ethyl acetate
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated