反应详情

Methyl 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate (97 mg, 0.50 mmol) was suspended in 4 mL of DCE and sequentially treated with DMAP (61 mg, 0.50 mmol) and triethylamine (0.077 mL, 0.55 mmol). Morpholine-4-sulfonyl chloride (102 mg, 0.55 mmol) was added and the mixture was stirred at ambient temperature for 2 hours and then heated to 50° C. for 2 days. The mixture was cooled to ambient temperature and diluted with 10 mL of DCM and the whole solution poured into 15 mL of 1M aqueous H3PO4. The layers were separated and the aqueous layer was extracted with 10 mL of DCM. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by normal phase flash chromatography (gradient elution 50% to 100% EtOAc/Hexanes) to provide 88 mg (51%) of the title compound as a thick tan oil. 1H NMR (CDCl3) δ 8.59 (d, 1H), 8.34 (d, 1H), 4.48 (m, 2H), 3.86 (s, 3H), 3.77 (m, 2H), 3.69 (m, 4H), 3.26 (m, 4H). LCMS (+ESI) m/z=344.1 [M+H]+.

1. temperatureheated to 50° C. for 2 days
2. temperatureThe mixture was cooled to ambient temperature
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with 10 mL of DCM
5. dry with materialThe combined organic phases were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by normal phase flash chromatography (gradient elution 50% to 100% EtOAc/Hexanes)