反应详情

4-(4-Methylsulfamoyl-4,7-diaza-spiro[2.5]oct-7-yl)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester (intermediate 4) (0.237 mmol) was dissolved in dry DMF (2 mL) and added Cs2CO3 (0.35 mmol) and 4-bromomethyl-benzonitrile (0.35 mmol). Stirred at rt for 16 h and then added H2O (10 mL). Extracted with EtOAc (3×10 mL) and the combined organic phases were concentrated in vacuo. Purified by flash chromatography on silica using a gradient of heptane to EtOAc as eluent. The obtained compound was treated with TFA (2 mL) at rt for 2 h. The crude reaction mixture was added sat. Na2CO3 to pH=7 and the extracted with EtOAc (3×10 mL). the combined organic phases was washes with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. The pure compound was obtained by trituation using CH2Cl2.

1. extractionExtracted with EtOAc (3×10 mL)
2. concentrationthe combined organic phases were concentrated in vacuo
3. customPurified by flash chromatography on silica using a gradient of heptane to EtOAc as eluent
4. additionThe obtained compound was treated with TFA (2 mL) at rt for 2 h
5. customThe crude reaction mixture
6. extractionthe extracted with EtOAc (3×10 mL)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe pure compound was obtained by trituation