1,8-Diazabicyclo(5.4.0)undec-7-ene → 7-Hydroxy-3-[4-methyl-5-(morpholine-4-carbonyl)-thiazol-2-yl]-chromen-2-one

To a stirred suspension of 7-hydroxy-2-oxo-2H-chromene-3-carbothioic acid amide (354 mg, 1.6 mmol) in anhydrous N,N-dimethylformamide (7 mL), 1,8-diazabicyclo-[5.4.0]undec-7-ene (480 μL, 490 mg, 3.2 mmol) was added followed by a solution of 2-bromo-1-morpholin-4-yl-butane-1,3-dione (750 mg, 3.0 mmol) in anhydrous N,N dimethylformamide (15 mL) and the mixture was stirred at room temperature for 15 h. The reaction mixture was poured into water (100 mL) and extracted first with chloroform (3×30 mL) then after saturation with NaCl, with tetrahydrofuran (3×50 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was dissolved in chloroform (16 mL), pyridinium p-toluenesulfonate (40.2 mg, 0.16 mmol) was added and the mixture was stirred at 60° C. for 4.5 h. The reaction mixture was washed with a mixture of brine (10 mL) and 5% NaHCO3 solution (5 mL) and then with brine (2×15 mL), dried over MgSO4 and concentrated. The residue was purified by column chromatography on silica, eluting with a 9:1:0.1 mixture of chloroform, methanol and cc. NH4OH. The title compound (34.6 mg, 0.093 mmol, 5.8%) was obtained as a yellow solid.

1. additionwas added
2. extractionextracted first with chloroform (3×30 mL)
3. dry with materialThe combined organic extracts were dried over MgSO4
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in chloroform (16 mL)
6. stirringthe mixture was stirred at 60° C. for 4.5 h
7. washThe reaction mixture was washed with a mixture of brine (10 mL) and 5% NaHCO3 solution (5 mL)
8. dry with materialwith brine (2×15 mL), dried over MgSO4
9. concentrationconcentrated
10. customThe residue was purified by column chromatography on silica
11. washeluting with a 9:1:0.1 mixture of chloroform, methanol and cc

ORD-Eintrag

ord-74f67ef9bd464658ba8cb1190a4eb841

Quelldatensatz

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09040714B2