Methanol → 7-(hydroxymethyl)-4-methyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one

Temperature

-45 °C

Methyl 4-methyl-2-oxo-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine-7-carboxylate (500 mg, 2.25 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, 136 mg, 3.40 mmol) and stirred 30 min. The reaction was then cooled to −45° C. and lithium aluminum hydride (2M in THF, 3.3 mL, 6.6 mmol) was added. The reaction was stirred at a temperature between −20 and −10° C. for 1 h. The reaction was then cooled back to −60° 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 (300 mL) and water (200 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 (3×100 mL). The organic layers were combined, washed with brine (100 mL), dried with sodium sulfate and concentrated to yield the title compound (415 mg, 95%) as a white solid. [M+H] calc'd for C9H11N3O2, 194; found, 194.

1. stirringThe reaction was stirred at a temperature between −20 and −10° C. for 1 h
2. temperatureThe reaction was then cooled back to −60° 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 (3×100 mL)
9. washwashed with brine (100 mL)
10. dry with materialdried with sodium sulfate
11. concentrationconcentrated

ORD record

ord-9360788446664a4db6d32675b7518459

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822470B2