2-Methoxyethylamine → HCID 57969164, compound

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) (8.66 g, 45.3 mmol) and 2-methoxy-ethylamine (15.6 mL, 181 mmol) in anhydrous dimethylformamide (40 mL) was heated to 60° C. for 7 h. The reaction was then cooled to room temperature. Dimethylformamide was azeotropically removed by the addition and evaporation of toluene (6×700 mL) by rotary evaporation with water bath at 70° C. An orange oil was obtained (12.2 g). The oil was fractionated by dry-pack column chromatography as follows: the oil was diluted with CH2Cl2 (400 mL) followed by the addition of silica gel (100 g, 230-400 mesh) and concentrated to dryness. This was loaded onto a silica column (200 g, 230-400 mesh) and eluted with 50% EtOAc/hexanes. Pure fractions were combined and concentrated to give the title compound as a white solid (5.37 g, 64% isolated yield). 1H NMR 400 MHz (d6-DMSO) δ7.79 (d, J=7.8 Hz, 1H), 7.30 (s, 1H), 6.76 (d, J=7.8 Hz, 1H), 6.52 (s, 1H), 4.04 (br t, J=4.7 Hz, 1H), 3.80 (td, J=5.5, 4.7 Hz, 2H), 3.63 (t, J=5.5 Hz, 2H), 2.94 (s, 3H).

1. customRefer to synthesis of D46
2. customA sealed reaction vessel
3. temperatureThe reaction was then cooled to room temperature
4. customDimethylformamide was azeotropically removed by the addition and evaporation of toluene (6×700 mL) by rotary evaporation with water bath at 70° C
5. customAn orange oil was obtained (12.2 g)
6. customby dry-pack column chromatography
7. additionthe oil was diluted with CH2Cl2 (400 mL)
8. additionfollowed by the addition of silica gel (100 g, 230-400 mesh)
9. concentrationconcentrated to dryness
10. washeluted with 50% EtOAc/hexanes
11. concentrationconcentrated

ORD record

ord-fd7c424fa3904bfd87f46cdc227038a5

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416146B2