反应详情

N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (71.4 mg, 0.37 mmol) was added portionwise to a stirred solution of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (85 mg, 0.19 mmol), 2-hydroxypyridine 1-oxide (41.4 mg, 0.37 mmol) and morpholine (0.033 mL, 0.37 mmol) at room temperature under nitrogen and stirred for 4 h. The reaction mixture was diluted with DCM, washed with water, brine, dried over MgSO4 and concentrated. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness, and the residue was dissolved in DCM, dried over MgSO4 and concentrated. The remaining solid was triturated with diethyl ether, filtered, washed with diethyl ether and dried under vacuum at 50° C. to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (58.0 mg, 59.3%) as a pale beige solid.

1. washwashed with water, brine
2. dry with materialdried over MgSO4
3. concentrationconcentrated
4. customThe reaction mixture was purified by preparative HPLC
5. customThe fractions were evaporated to dryness
6. dissolutionthe residue was dissolved in DCM
7. dry with materialdried over MgSO4
8. concentrationconcentrated
9. customThe remaining solid was triturated with diethyl ether
10. filtrationfiltered
11. washwashed with diethyl ether
12. customdried under vacuum at 50° C.