Dimethylformamide → 5-((Tert-butyldiphenylsilyl)oxy)-5,6,7,8-tetrahydro-1,8-naphthyridine-2-carbaldehyde

Temperature

-78 °C

A solution of 7-bromo-4-((tert-butyldiphenylsilyl)oxy)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 72, 400 mg, 0.856 mmol) in THF (6 ml) at −78° C. was treated with n-BuLi (1.6 M in hexane, 1.34 ml, 2.14 mmol). The reaction mixture was stirred 15 min at −78° C. and then, the solution was warmed up to −20° C. and stirred at this temperature for 30 min. The mixture was then cooled to −78° C., treated with DMF (0.66 mL, 8.6 mmol), stirred at −78° C. for 15 min and then warmed up to −20° C. and stirred at −20° C. for 30 min. The reaction was quenched with water and extracted with DCM (3×). The organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified by normal phase chromatography (heptanes/EtOAc) to give the title compound as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 9.66-9.71 (m, 1H), 7.63-7.69 (m, 2H), 7.43-7.56 (m, 6H), 7.35-7.42 (m, 2H), 7.21 (br. s., 1H), 7.01 (d, 1H), 6.88 (d, 1H), 4.80-4.85 (m, 1H), 3.43-3.52 (m, 1H), 3.23-3.31 (m, 1H), 1.77-1.87 (m, 1H), 1.56-1.67 (m, 1H), 1.00 (s, 9H).

1. temperaturethe solution was warmed up to −20° C.
2. stirringstirred at this temperature for 30 min
3. temperatureThe mixture was then cooled to −78° C.
4. stirringstirred at −78° C. for 15 min
5. temperaturewarmed up to −20° C.
6. stirringstirred at −20° C. for 30 min
7. customThe reaction was quenched with water
8. extractionextracted with DCM (3×)
9. dry with materialThe organic layer was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customThe crude material was purified by normal phase chromatography (heptanes/EtOAc)

ORD record

ord-70f7541bd6c442da9776f1d3c4154d4a

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266883B2