2-Cyano-5-fluoropyridine

5-Fluoro-pyridine-2-carbonitrile; Sodium nitrite (8.7g, 126 mmol) was added portionwise to an ice-salt cooled solution of 5- amino-pyridine-2-carbonitrile (10.03g, 84.2 mmol) in 70percent hydrogen fluoride-pyridine (Aldrich, 100g, 3.5 mol HF) (note: the reaction was carried out in the supplied bottle). The resulting dark red solution was stirred for 45 min in the ice-salt bath, then the bath was re- moved and the mixture stirred at ambient temperature for 30 min, followed by heating at 80°C for 1. 5h. The reaction mixture was quenched by pouring onto ice/water mixture (-400g) in a separatory funnel and extracted with dichloromethane (6xl 50mL), dried (MgS04), filtered and evaporated the solvent in vacuo. The crude product (10.08g, 98percent, orange solid) was sufficiently pure for use without further purification. lH NMR (CDC13, 300 MHz): 8 = 8.61 (d, 1H), 7. 78 (m, 1H), 7.58 (m, 1H). GC-MS M+122.1) To hydrogen fluoride - pyridine (100 ml) was added 5-amino-2-cyanopyridine (24.5 g, 0.206 mol) under ice cooling. The resulting mixture was stirred for 10 minutes. To the reaction mixture was added sodium nitrite (15.6 g, 0.226 mol). The resulting mixture was stirred at room temperature for 10 minutes, and then stirred at 50°C for 2 hours. To the reaction mixture was added a 20percent aqueous solution of sodium hydroxide. The resulting mixture was extracted with diethyl ether. The organic layer thus obtained was dried over sodium sulfate, and concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography. The fraction obtained from the hexane:ethyl acetate=3:1 eluate was concentrated under reduced pressure to give the title compound (16.0 g, 0.131 mmol, 64percent) as colorless needle crystals. 1) 5-Fluoropyridine-2-carbonitrile 5-Amino-2-cyanopyridine (24.5 g) was added to hydrogen fluoride-pyridine (100 mL) under ice cooling, and the resultant mixture was stirred for 10 minutes. Sodium nitrite (15.6 g) was added to the reaction solution, and the mixture was stirred at room temperature for 10 minutes, and then stirred at 50°C for 2 hours. After air cooling, a 20percent aqueous solution of sodium hydroxide and diethyl ether were added to the reaction solution, and the resultant mixture was partitioned. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and a residue thus obtained was purified by silica gel column chromatography (hexane-ethyl acetate), to obtain 5-fluoropyridine-2-carbonitrile (16.0 g, 64percent) as a solid. To a 100 mL round bottom flask charged with 5-aminopicolinonitrile (285 mg, 2.44 mmol) at 0° C. was added HF-pyridine (5 mL) under NA mixture of 2-bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), dppf (11.7 g, 21.1 mmol) and Pd2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), diphenylphosphinoferrocene (11.7 g, 21.1 mmol) and PdIntermediate 25-Fluoropyridine-2-carbonitrile2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), dppf (11.7 g, 21.1 mmol) and Pd2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), l, r-bis(diphenylphosphino)ferrocene (11.7 g, 21.1 mmol) and PdIntermediate 1: 5-Fluoropyridine-2-carbonitrile. 2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), l , l'-bis(diphenylphosphino)ferrocene (1 1.7 g, 21.1 mmol) and PdIntermediate 35-Fluoropyridine-2-carbonitrile; 2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), l, l'-bis(diphenylphosphino)ferrocene (11.7 g, 21.1 mmol) and Pd2dbaIntermediate 115-Fluoropyridine-2-carbonitrile2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, Intermediate 15-Fluoropyridine-2-carbonitrile; 2-Bromo-5-fluoropyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), l, l'-bis(diphenylphosphino)ferrocene (11.7 g, 21.1 mmol) and Pd2-Bromo-5-fluoiOpyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), l, r-bis(diphenylphosphino)ferrocene (11.7 g, 21.1 mmol) and PdPreparation 84; 2-Cyano-5-fluoropyridine; Add in a 5-L 3-neck roundbottom equipped with overhead stirrer, reflux condenser, thermometer, and N2 line, 5-chloro-2-cyanopyridine (193.0 g, 1. 39 mol) and 1-methyl-2-pyrrolidinone (NMP, 2L). Heat the mixture and stir at 210-220 ° C for 4 h. Cool the reaction mixture to room temperature, stir overnight, and filter. Wash the filter cake with ethyl ether (1L). Extract the filtrate with water (6L) and ethyl ether (3 X 5L). Combine the organics and back-extract with water (8L) and dry over magnesium sulfate. Concentrate at 25-30 ° C to give an oily semi-solid, 193 g. Chromatograph over flash silica gel (5percent ethyl acetate in hexanes gradually increasing to 10percent ethyl acetate in hexanes) to provide the title compound as a white solid. Dissolve the solid in ethyl ether, filter, and add hexanes. Concentrate to low volume to provide a primary crop of pure title compound, 60 g. Repeat the process of crystallization on the filtrate to provide a second crop of highly pure title compound, 24.0 g. (Concentrate the final filtrate to a white solid of product of good quality, and re-chromatograph, conditions as above, to provide an additional 38.6 g of material. ) Obtain a total yield of title compound of 122.4 g, 72percent ; 1H NMR (CDCl3) 5 8.59 (d, J= 3.0 Hz, 1H), 7.75 (m, 1H), 7.55 (m, 1H).A mixture of 2-cyano-5-chloropyridine (1 g, 7.22 mmol) and potassium fluoride (1.26 g, 21.68 mmol) in 1-methyl-2-pyrrolidinone (25 mL) was heated at reflux for 18 hours. 10(A) 5-Fluoro-pyridine-2-carbonitrile; A solution of 2-bromo-5-fluoro-pyridine (5.0 g, 28.4 mmol), CuCN (2.01 g, 22.5 mmol) and NaCN (1.14 g, 23.2 mmol) in dry DMF (50 ml) was refluxed for 9h. The reaction mixture was allowed to cool down to room temperature and a solution of 2percent K2-Bromo-5-fluoiOpyridine (93.0 g, 528 mmol), Zn dust (8.29 g, 127 mmol), zinc cyanide (40.3 g, 343 mmol), l, r-bis(diphenylphosphino)ferrocene (11.7 g, 21.1 mmol) and Pd

Molecular Weight:122.10
XLogP3:1
Hydrogen Bond Acceptor Count:3
Exact Mass:122.02802627
Monoisotopic Mass:122.02802627
Topological Polar Surface Area:36.7
Heavy Atom Count:9
Complexity:137
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes