Methyl iodide → (S)-tert-butyl methyl(4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

Temperature

0 °C

To a solution of (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (200 mg, 0.470 mmol) (Preparation description in Example 2, Part D) in THF (4 mL) at 0° C. was added NaH (37.6 mg, 0.940 mmol). The reaction was stirred at 0° C. for 30 min then MeI (0.044 mL, 0.705 mmol) was added. The reaction mixture was then stirred at 0° C. for 16 h. The reaction mixture was quenched with ice cold water (50 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers and washed with brine (1×50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate mobile phase to afford (S)-tert-butyl methyl(4-methyl-1-(6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yloxy)pentan-2-yl)carbamate (180 mg, 0.409 mmol, 87% yield) as a yellow solid. LC/MS (ESI) m/e 440.4, [(M+H)+, calcd for C25H34N3O4, 440.3]; LC/MS retention time (method I): tR=2.4 min.

1. stirringThe reaction mixture was then stirred at 0° C. for 16 h
2. customThe reaction mixture was quenched with ice cold water (50 mL)
3. extractionextracted with ethyl acetate (3×30 mL)
4. washThe combined organic layers and washed with brine (1×50 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude product was purified by silica gel chromatography

ORD record

ord-b21a33d6efa44816b9c064788e7585b7

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2