Sodium hydride → 7-(hydroxymethyl)-4-isopropyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one

温度

0 °C

Methyl 4-isopropyl-2-oxo-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine-7-carboxylate (1.3 g, 5.45 mmol) was suspended in tetrahydrofuran (68 mL). The white suspension was cooled to 0° C. and NaH (60% dispersion in mineral oil, 0.327 g, 8.17 mmol) was added. The reaction was removed from the ice bath and allowed to stir at RT for 0.5 h. The solution was then cooled to −78° C. and LiAlH4 was added over two min. A temperature between −30 and −20° C. was maintained. The reaction was cooled to −78° C. and MeOH (2 mL) was added. The reaction was stirred at room temperature 30 min. The reaction was poured into ethyl acetate (400 mL) and water (100 mL), and stirred for 1 hr. The mixture was filtered through medium frit to remove tan solids. The aqueous layer was extracted with ethyl acetate (1×100 mL). The organic fractions were combined, washed once with brine (100 mL), dried with sodium sulfate and concentrated to the title compound (1.10 g, 91%) as a white solid. [M+H] calc'd for C11H15N3O2, 222; found, 222.

1. customThe reaction was removed from the ice bath
2. temperatureThe solution was then cooled to −78° C.
3. additionLiAlH4 was added over two min
4. temperatureA temperature between −30 and −20° C. was maintained
5. temperatureThe reaction was cooled to −78° C.
6. additionMeOH (2 mL) was added
7. stirringThe reaction was stirred at room temperature 30 min
8. additionThe reaction was poured into ethyl acetate (400 mL) and water (100 mL)
9. stirringstirred for 1 hr
10. filtrationThe mixture was filtered through medium frit
11. customto remove tan solids
12. extractionThe aqueous layer was extracted with ethyl acetate (1×100 mL)
13. washwashed once with brine (100 mL)
14. dry with materialdried with sodium sulfate
15. concentrationconcentrated to the title compound (1.10 g, 91%) as a white solid

ORDレコード

ord-3544676cf4a944f79be27f3d11fa2717

出典データセット

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07928105B2