2-fluoro-N-methoxy-N,5-dimethylnicotinamide → Tert-butyl 4-(6-(2-fluoro-5-methylnicotinoyl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

Temperatur

-78 °C

To a solution of tert-butyl 4-(6-bromopyridin-2-yl)-1,4-diazepane-1-carboxylate (898 mg, 2.52 mmol) in tetrahydrofuran (10 ml) at −78° C. was added a 2.5M solution of nbutyllithium in hexanes (1.01 ml, 2.52 mmol) dropwise maintaining the temperature at −78° C. After complete addition, the solution was stirred at −78° C. for a further 20 minutes. A solution of 2-fluoro-N-methoxy-N,5-dimethylnicotinamide (500 mg, 2.52 mmol) in tetrahydrofuran (5 ml) was added dropwise at −78° C. and the reaction mixture was stirred at −78° C. for 1 hour. The reaction was quenched with a saturated solution of ammonium chloride. The mixture was stirred at room temperature for 20 minutes and extracted into ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 40 g column, 0-20% EtOAc/Petrol) to afford the title compound as a sticky green oil (906 mg, 87% yield).

1. additionAfter complete addition
2. stirringthe reaction mixture was stirred at −78° C. for 1 hour
3. customThe reaction was quenched with a saturated solution of ammonium chloride
4. stirringThe mixture was stirred at room temperature for 20 minutes
5. extractionextracted into ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified on silica gel by flash column chromatography (ISCO Companion□, 40 g column, 0-20% EtOAc/Petrol)

ORD-Eintrag

ord-5cfdfa8bc479410ba24d98435c04a36b

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08188071B2