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1373940-69-2

5-Chloro-N-(2,6-difluorophenyl)pyrazine-2-carboxamide synthesis

3synthesis methods
34604-60-9 Synthesis
5-Hydroxypyrazine-2-carboxylic acid

34604-60-9
202 suppliers
$15.00/1g

5-Chloro-N-(2,6-difluorophenyl)pyrazine-2-carboxamide

1373940-69-2
5 suppliers
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Yield:-

Reaction Conditions:

Stage #1: 5-hydroxypyrazinoic acidwith thionyl chloride;N,N-dimethyl-formamide for 15 h;Reflux;
Stage #2: 2,6-difluoroanilinewith triethylamine in tetrahydrofuran at 0 - 20; for 3 h;

Steps:

121.1

Example 121 Step-1 : 5-Chloro-N-(2,6-difluorophenyl)pyrazine-2-carboxamide: A mixture of 5- hydroxypyrazine-2-carboxylic acid (500 mg, 3.57 mmol, 1.0 eq), thionyl chloride (5 mL) and DMF (0.3 mL) was refluxed for 15 h. The excess of thionyl chloride was removed under vacuum and the residue was taken in THF (5 mL). The resulting mixture was cooled to 0 °C and a solution of 2,6-difluoroaniline (0.58 mL, 5.35 mmol, 1.5 eq) was added to the above mixture followed by triethyl amine (0.75 mL, 5.35 mmol, 1.5 eq). After stirring for 3 h at room temperature, the reaction was diluted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), 2N HC1 (10 mL), dried (Na2S04) and filtered. The filtrate was concentrated under vacuum. The crude product was purified with flash column chromatography (silica gel, ethyl acetate and hexane system as eluent) to afford 500 mg of the title product as a white solid. 1HNMR (400 MHz, DMSO-c?) δ 10.67 (s, 1H, D20 exchangeable), 9.1 1 (s, 1H), 9.98 (s, 1H), 7.47-7.41 (m, 1H), 7.26-7.21 (m, 2H); ESI-MS (m/z) 270, 272 [(MH)+, CI 35> 37]

References:

WO2012/56478,2012,A1 Location in patent:Page/Page column 124-125