Methyl iodide → 2-anilino-7-chloro-6-fluoro-5-methyl-1-phenyl-1,8-naphthyridin-4(1H)-one

Temperature

-40 °C

A solution of LTMP [freshly prepared at 0° C. from tetramethylpiperidine (227.2 mg, 1.62 mmol), TMEDA (188.3 mg, 1.62 mmol) and n-BuLi (1 mL, 1.62 mmol)] in THF (5 mL) was added to a cooled (−40° C.) and stirred solution of 2-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one (200 mg, 0.54 mmol) in THF (10 mL). The reaction mixture was warmed to 0° C., for 1 h and then re-cooled to −40° C. MeI (766 mg, 5.35 mmol) was added and the reaction mixture was allowed to warm to room temperature and was stirred overnight. The reaction was quenched carefully with water (50 mL) and then extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. Silica gel flash chromatography of the residue using 1:1 EtOAc:Hex afforded 2-anilino-7-chloro-6-fluoro-5-methyl-1-phenyl-1,8-naphthyridin-4(1H)-one (184 mg, 88%) as a white solid: LCMS RT: 2.74 min, MH+: 380.3. This transformation can also be accomplished by using other amide bases such as LDA.

1. additionwas added to
2. temperatureThe reaction mixture was warmed to 0° C., for 1 h
3. temperaturere-cooled to −40° C
4. temperatureto warm to room temperature
5. customThe reaction was quenched carefully with water (50 mL)
6. extractionextracted with EtOAc
7. washThe combined organic extracts were washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo

ORD record

ord-8fe3fae508e847d78a37736af8cc892b

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06964971B2