Methanol → 3-(hydroxymethyl)-6a,7,9,10-tetrahydropyrido[3,2-e][1,4]thiazino[4,3-a]pyrazin-6(5H)-one

Temperature

-78 °C

Methyl 6-oxo-5,6,6a,7,9,10-hexahydropyrido[3,2-e][1,4]thiazino[4,3-a]pyrazine-3-carboxylate (386 mg, 1.38 mmol) was taken up in tetrahydrofuran (25 mL) in an inert environment. To the stirred suspension at room temperature was added NaH (60% dispersion in mineral oil, 121 mg, 3.03 mmol) and stirred 30 min. The reaction was cooled to −78° C. and lithium aluminum hydride (3 mL, 2M in THF) was added. The reaction was stirred at a temperature between −20 and −10° C. for 3 h. The reaction was cooled back to −78° C. and MeOH (1 mL) followed by water (1 mL) was added. The reaction was allowed to stir at ambient temperature for 2 h and then poured into ethyl acetate (200 mL) and water (100 mL). The biphasic mixture was stirred vigorously and then filtered through a medium frit. The layers were separated and the aqueous phase was extracted with ethyl acetate (2×50 mL). The organic layers were combined, washed with brine (100 mL), dried with sodium sulfate and concentrated to afford the title compound (497 mg, 98%) as a white solid. [M+H] calc'd for C11H13N3O2S, 252; found, 252.

1. stirringThe reaction was stirred at a temperature between −20 and −10° C. for 3 h
2. temperatureThe reaction was cooled back to −78° C.
3. additionwas added
4. stirringto stir at ambient temperature for 2 h
5. stirringThe biphasic mixture was stirred vigorously
6. filtrationfiltered through a medium frit
7. customThe layers were separated
8. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
9. washwashed with brine (100 mL)
10. dry with materialdried with sodium sulfate
11. concentrationconcentrated

ORD record

ord-b2550ae36288472fab41911a31ba5d50

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822470B2