反应详情

温度

110 °C

Dissolve 4-[1,3]dioxolan-2-yl-2-phenol (Example 388, Part C2) (1.70 g, 10.2 mmol), 5-chloropyrazine-2-carbonitrile (Example 404, Part A) (1.50 g, 10.7 mmol) and K2CO3 (3.71 g, 26.9 mmol) in DMA (27.0 mL) and isooctane (13.4 mL). Heat at 110° C. for about 2.25 hours. Cool to room temperature and quench with water (100 mL). Extract with dichloromethane (3×100 mL). Wash the extract with saturated aqueous NaHCO3 (1×50 mL) and brine (1×75 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography, eluting with 0-30% ethyl acetate in hexanes. Concentrate the eluant, then take the solid up in 88% formic acid (46 mL) and stir at room temperature for 4 hours. Dilute the reaction mixture with water (50 mL). Extract with dichloromethane (2×100 mL). Wash the extract with saturated aqueous NaHCO3 (1×50 mL), dry over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 30% ethyl acetate in hexanes to give the title compound (1.88 g, 77.7%): TOF MS ES+ 225.1 (M)+, HRMS calcd for C12H7N3O2 225.0538 (M)+, found 225.0527, time 0.38 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 20-99% over 23 min], tR=11.5 min, 100% purity.

1. temperatureCool to room temperature
2. customquench with water (100 mL)
3. extractionExtract with dichloromethane (3×100 mL)
4. washWash the
5. extractionextract with saturated aqueous NaHCO3 (1×50 mL) and brine (1×75 mL)
6. dry with materialDry the organic layer over Na2SO4
7. filtrationfilter
8. concentrationconcentrate
9. customPurify by flash chromatography
10. washeluting with 0-30% ethyl acetate in hexanes
11. concentrationConcentrate the eluant
12. additionDilute the reaction mixture with water (50 mL)
13. extractionExtract with dichloromethane (2×100 mL)
14. washWash the
15. extractionextract with saturated aqueous NaHCO3 (1×50 mL)
16. dry with materialdry over Na2SO4
17. filtrationfilter
18. concentrationconcentrate
19. customPurify by flash chromatography
20. washeluting with 30% ethyl acetate in hexanes