反应详情

A mixture of 2-(dimethoxymethyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepine (intermediate 237, 35 mg, 0.154 mmol), phenyl(5-cyanopyridin-2-yl)carbamate (intermediate 240, 122 mg, 0.509 mmol) and DMAP (28.3 mg, 0.231 mmol) in THF (1.7 ml) was heated at reflux for 23 h. The reaction mixture was diluted with sat. aq. NaHCO3 and extracted with DCM (3×). The combined organic layers were dried over Na2SO4 and evaporated. The crude material was applied to a 40 g RediSep® silica column and purified by normal phase chromatography, eluting with 99:1 DCM/MeOH. Product-containing fractions were combined and evaporated. The residue was triturated with Et2O and the solid removed by filtration. The filtrate was concentrated and the residue triturated with MeOH to give the title compound as a white solid. (UPLC-MS 6) tR 1.06; ESI-MS 368.1 [M+H]+.

1. temperaturewas heated
2. temperatureat reflux for 23 h
3. extractionextracted with DCM (3×)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. customevaporated
6. custompurified by normal phase chromatography
7. washeluting with 99:1 DCM/MeOH
8. customevaporated
9. customThe residue was triturated with Et2O
10. customthe solid removed by filtration
11. concentrationThe filtrate was concentrated
12. customthe residue triturated with MeOH