Morpholine → 6-Chloro-2-[2-(4-morpholinyl)ethyl]-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxide

To a solution of the product from Step A (0.76 g, 2.20 mmol) in tetrahydrofuran (30 mL) containing triethylamine (0.56 g, 5.5 mmol) was added methanesulfonic anhydride (0.75 g, 4.3 mmol); this mixture was stirred at room temperature for 1 hr and evaporated to dryness. The residue was dissolved in DMF (30 mL), triethylamine (1 mL) was added and the mixture heated at 150° C. for 45 min. Morpholine (3 mL, 34 mmol) was added to the reaction mixture and heating continued at the same temperature for 1 hr followed by heating at 100° C. for an additional hour. The volatiles were evaporated and the residue mixed with ethyl acetate; this mixture was washed with saturated aqueous sodium bicarbonate, dried (MgSO4) and evaporated to an oil which was purified by column chromatography (silica, 50% ethyl acetate/hexane to ethyl acetate) to give a viscous oil (0.42 g, 58%) which was used in the next step.

1. customevaporated to dryness
2. dissolutionThe residue was dissolved in DMF (30 mL)
3. additiontriethylamine (1 mL) was added
4. temperaturethe mixture heated at 150° C. for 45 min
5. temperatureheating
6. waitcontinued at the same temperature for 1 hr
7. temperatureby heating at 100° C. for an additional hour
8. customThe volatiles were evaporated
9. additionthe residue mixed with ethyl acetate
10. washthis mixture was washed with saturated aqueous sodium bicarbonate
11. dry with materialdried (MgSO4)
12. customevaporated to an oil which
13. customwas purified by column chromatography (silica, 50% ethyl acetate/hexane to ethyl acetate)

ORD-Eintrag

ord-38f03d781f3947ca8eb2fe0545b40a67

Quelldatensatz

uspto-grants-1996_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05538966