反应详情

温度

45 °C

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) (0.71 mmol) was dissolved in dry DMF (0.5 mL) and added Cs2CO3 (1.42 mmol) and tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate (0.85 mmol). Stirred at 45° C. for 16 h and then added H2O (2 mL). Extracted with EtOAc (3×2 mL) and the combined organic phases were concentrated in vacuo. The residual oil was treated with a mixture of 1,1,1,3,3,3-hexafluoro-2-propanol: 2,2,2-trifluoroethanol (3:1, 4 mL) at 150° C. for 2 h. The crude reaction mixture was concentrated on celite in vacuo and purified by standard column chromatography using methanol in DCM as eluent. The obtained compound was recrystallized in methanol:EtOAc affording the title compound as solid.

1. extractionExtracted with EtOAc (3×2 mL)
2. concentrationthe combined organic phases were concentrated in vacuo
3. additionThe residual oil was treated with a mixture of 1,1,1,3,3,3-hexafluoro-2-propanol: 2,2,2-trifluoroethanol (3:1, 4 mL) at 150° C. for 2 h
4. customThe crude reaction mixture
5. concentrationwas concentrated on celite in vacuo
6. custompurified by standard column chromatography
7. customThe obtained compound was recrystallized in methanol