反应详情

TBTU (176 mg, 0.55 mmol) was added in one portion to a stirred solution of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (125 mg, 0.27 mmol) and DIPEA (0.286 mL, 1.64 mmol) at room temperature and stirred for 2.5 h. Thiomorpholine 1-oxide hydrochloride (85 mg, 0.55 mmol) was added to the reaction mixture and stirring was continued for 3 h. The reaction mixture was diluted with DCM, washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by preparative HPLC. The fractions were evaporated to dryness, 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]-2-morpholino-6-(1-oxo-1,4-thiazinane-4-carbonyl)chromen-4-one (87 mg, 57%) as a pale beige solid.

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