2-Cyano-5-nitropyridine

Green Solid

A mixture of 2-bromo-5-nitropyridine (12.0 g, 59.1 mmol, CAS No.: 4487-59-6) and copper (I) cyanide (7.94 g, 88.7 mmol) in N, N-dimethylformamide (50 mL) was heated under reflux for 16 hours. After being cooled down to room temperature, the reaction mixture was poured into water and then extracted with ethyl acetate (100 mL x 3). The combined organiclayer was washed with brine, and then dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford 8.0 g of 5-nitropyridine-2-carbonitrile (yield was 90.8percent).Step A: 5-Nitropicolinonitrile (20) [00383] A mixture of 2-bromo-5-nitropyridine (19) (10 g, 50 mmol) and CuCN (8.9 g, 100 mmol) in DMF (25 mL) was stirred at 100°C for 2 h. The reaction mixture was then cooled to room temperature and diluted with DCM (200 mL). Solid was filtered; the filtrated was then concentrated and purified by silica gel column chromatography with petroleum ether/ ethyl acetate (3 : 1) to give the product (3 g, 40percent) as a yellow solid. LC-MS: (M + H)Synthesis of compound E; Copper cyanide (I) (662 mg, 7.34 mmol) and sodium cyanide (I) (242 mg, 4.93 mmol) were dissolved in N, N-dimethylformamide (7.5 ml), and the solution was stirred at 150°C for 25 minutes. A solution of 2-bromo-5-nitropyridine (113 mg, 0.700 mmol) completely dissolved in N, N-dimethylformamide (2.5 ml) at 100°C was added to the solution, and the mixture was stirred with heating at 150°C for 100 minutes. The completion of the reaction was confirmed using a TLC plate (ethyl acetate:hexane = 1:3), and the reaction was terminated with 10 ml of an aqueous solution of 1 M monopotassium phosphate, followed by extraction with ethyl acetate (50 ml .x. 3). The ethyl acetate layer was washed with water (100 ml) and with saturated saline (100 ml). The resultant was dried over magnesium sulfate and filtered, followed by removal of a solvent by distillation under reduced pressure. The product was separated via flash column chromatography (ethyl acetate:hexane = 1:7 --> 1:3) to obtain a yellow, oil-like target compound E (624 mg, 4.19 mmol). Yield: 85percent 1) first equipped with a mechanical stirrer 30L glass reactor was added 7616mL dimethylformamide and612.8gNaCN and 1680gCuCN configured as a cyanide solution, The oil bath was then heated to 142 ° C, Continue to cyanide solution was added at a temperature of 80 ° C, A solution of 2-bromo-5-nitropyridine in dimethylformamide, Among them, 2-bromo-5-nitropyridine and dimethylformamide were 2538.6g and 5077mL respectively, And add within 5min, After adding at 160 reaction temperature, the reaction was 5.5h.2) After the reaction is completed, the temperature is lowered to 125 DEG C, 5757.5g of KH2PO4 buffer consisting of KH2PO4 and 42.2L of water are added, Keep the temperature of the mixture at 80 ~ 85 ° C for 1 h and cool to room temperature.3) The reaction mixture in step 2) was filtered, and the filtrate and filter cake were separated: the filtrate was extracted with 10 L of ethyl acrylate 3Times; the same filter cake was filtered after beating with ethyl acrylate, the two combined organic phase, and concentrated to 20L with KH2PO4 slowThe solution was washed sequentially with 14 L of water; the washed buffer and the aqueous layer were extracted twice more with 5 L of ethyl acrylate, and the combined organic phases were concentratedThe yield was 1935 g of 2-cyano-5-nitropyridine as an orange solid with a purity of 97percent and a yield of 103.8percent.

A useful synthetic intermediate

Molecular Weight:149.11
XLogP3:1.3
Hydrogen Bond Acceptor Count:4
Exact Mass:149.022526347
Monoisotopic Mass:149.022526347
Topological Polar Surface Area:82.5
Heavy Atom Count:11
Complexity:202
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes