5,6-DICHLORONICOTINAMIDE synthesis

Yield:75291-84-8 95%

Reaction Conditions:

Stage #1: 5,6-dichloronicotinic acidwith thionyl chloride;N,N-dimethyl-formamide in tetrahydrofuran at 50; for 2.5 h;
Stage #2: with ammonia in tetrahydrofuran;water at 0 - 20;

Steps:

2.1 2.1 Intermediate 1

5,6-dichloropyridine-3-carboxylic acid (33 g, 0.17 mol) is dissolved in 310 mL of THF. To this solution thionyl chloride (26.2 mL, 0.22 mol) is added. Then 0.17 mL of DMF is added. The reaction mixture is stirred for 2.5h at 50°C. After cooling to room temperature, the reaction mixture is poured into 390 mL of a concentrated ammonia solution (25%) and 500 mL of water. The mixture is cooled to 0°C and stirred overnight to room temperature. The THF is reduced under vacuum, the aqueous solution is extracted with ethyl acetate. The organic layer is washed with water, followed by a sodium hydroxide solution (10%). After drying over anhydrous sodium sulfate the solvent is reduced. The residue is dried under vacuum to give 30.9 g of the desired product in 95% yield. H-NMR (DMSO): δ = 7.83 (s, 1 H), 8.28 (s, 1 H), 8.49 (s, 1 H), 8.81 (s, 1 H).

References:

WO2015/150203,2015,A1 Location in patent:Page/Page column 74