Pyridine → 2,6-Dichloropyridine-3-carboxamide

Experimental procedure for synthesis of 6-chloro-2-morpholin-4-yl-nicotinonitrile (3) is the same as that described in synthesis of (D46). The reaction of 6-chloro-2-morpholin-4-yl-nicotinamide (2) (2.49 g) with phosphorus oxychloride (2.7 mL, 29 mmol) and pyridine (4.7 mL, 58 mmol) in acetonitrile (60 mL) gave a crude black oil upon workup. The black oil was fractionated by dry-pack column chromatography as follows: the oil was diluted with CH2Cl2 (300 mL) followed by the addition of silica gel (20 g, 230-400 mesh) and concentrated to dryness. This was loaded onto a silica column (60 g, 230-400 mesh) and eluted with 10% EtOAc/hexanes. Pure fractions were combined and concentrated to give the title compound as a white solid (1.97 g, 91% isolated yield over 2 steps with respect to 1.85 g of compound 1). TLC eluted with 50% EtOAc/hexanes and rendered with UV lamp gave Rf=0.8; 1H NMR 400 MHz (CDCl3) δ 7.69 (d, J=8.2 Hz, 1H), 6.75 (d, J=7.8 Hz, 1H), 3.85-3.77 (8H).

1. customthat described in synthesis of (D46)
2. customgave a crude black oil upon workup
3. customby dry-pack column chromatography
4. additionthe oil was diluted with CH2Cl2 (300 mL)
5. additionfollowed by the addition of silica gel (20 g, 230-400 mesh)
6. concentrationconcentrated to dryness
7. washeluted with 10% EtOAc/hexanes
8. concentrationconcentrated

ORD record

ord-d0d42bd0b1d74338a9e878a075ca976e

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416146B2