反应详情

A mixture of (7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (163 mg, 0.546 mmol, 1.0 equiv), 5-amino-2-(4-isopropylpiperazin-1-yl)benzonitrile (200 mg, 0.819 mmol, 1.5 equiv), and PTSA monohydrate (208 mg, 1.09 mmol, 2.0 equiv) in IPA (5 mL) was heated to reflux for 2 days. After cooling to ambient temperature, the crude mixture was concentrated to dryness and taken in water, EtOAc, and 1N NaOH. The layers were separated. The organic layer was washed with 1N NaOH 1×, dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH=100:0 to 95:5 using 1% 2M NH3/MeOH increments to give Compound 138 (195 mg, 71% yield) as a solid.

1. temperaturewas heated
2. temperatureto reflux for 2 days
3. concentrationthe crude mixture was concentrated to dryness
4. customThe layers were separated
5. washThe organic layer was washed with 1N NaOH 1×
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated to dryness
9. customThe crude product was purified by flash chromatography
10. washeluted with DCM