Methylamine → 6-Chloro-2-(methylamino)-3-pyridinecarboxamide

Temperature

60 °C

Refer to synthesis of D46 for preparation of 2,6-dichloro-nicotinamide (1). A sealed reaction vessel containing 2,6-dichloro-nicotinamide (1) (6.23 g, 32.6 mmol) and methylamine (98 mL of 2M in THF, 196 mmol) in anhydrous dimethylformamide (60 mL) was heated to 60° C. for 4 h. The reaction was then cooled to room temperature and diluted with water (800 mL) and extracted with ethyl acetate (4×600 mL). All organics were combined, dried over Na2SO4, filtered and concentrated to give a light orange oil (7.10 g). The oil was diluted with CH2Cl2 (300 mL) followed by the addition of silica gel (50 g, 230-400 mesh) and concentrated to dryness. This was loaded onto a silica column (200 g, 230-400 mesh) and eluted with gradient 30-50% EtOAc/hexanes. Pure fractions were combined and concentrated to give the title compound as a white solid (4.73 g, 78% isolated yield). TLC eluted with 50% EtOAc/hexanes and rendered with UV lamp gave Rf=0.5; 1H NMR 400 MHz (CDCl3) δ 7.47 (d, J=8.5 Hz, 1H), 7.90 (d, J=7.9 Hz, 1H), 1.48 (s, 3H).

1. customRefer to synthesis of D46
2. customA sealed reaction vessel
3. temperatureThe reaction was then cooled to room temperature
4. extractionextracted with ethyl acetate (4×600 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-3c55b629cfda4e35984f306b25f25e6f

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416146B2