5-(2-Fluorophenyl)-1H-pyrrole-3-carbonitrile

(2)(2)A stainless steel SUS316 high pressure reactor (trickle bed reactor, inner diameter 9 mm, length 490 mm) was filled with 12 g of a 1percent palladium alumina catalyst. Example 482 g of the intermediate IV-1 was dissolved in 40 ml of methanol, 200 mg of 10percent palladium on carbon was added, hydrogen gas was introduced, and the reaction was stirred at room temperature overnight. After the reaction was completed, it was suction filtered with a celite funnel containing celite, and the filtrate was concentrated to give compound of formula V-1, 1.65 g of white solid, yield 98percentCompound (3) (8.36g, 37.9mmol), absolute ethanol (100ml), triethylamine (5.0g, 49.3mmol), and 10percent palladium carbon (water content 60percent, 1.05g, 0.5percent w / w) was added to the reaction flask. The hydrogen gas (0.1MPa) was feeded into the system, and the reaction was stirred for 12 hours. After completion of the reaction, nitrogen was purged, and the reaction solution was filtered and washed with ethanol (15ml × 2). The filtrate was evaporated to about 20 ml, and water (45 ml) was added thereto, stirred at room temperature for 1 hour, and stirred at 0 to 5 ° C for 1 hour. After the solution was filtered, the filter cake was washed with water (15 ml). The filter cake was collected and dried under reduced pressure to give a yellow solid (6.62 g, yield 93.8percent).Example 2The reaction flask was added with 1.5 kg of the compound, Anhydrous ethanol 6 kg stir to completely dissolved, Adding 1.15 kg of diisopropylethylamine and 100 g of palladium on carbon with a mass fraction of 5percent (Dry basis weight 50 grams), The reaction was carried out at 45 ° C for 10 hours. The palladium-carbon was removed by filtration and rinsed with about 1 kg of ethanol. The majority of the solvent (product did not precipitate) was concentrated and the crystals were slowly added dropwise with 6 kg of water. 5 ° C for 1 hour, filtered and dried at 50 ° C to give a solid product.Example 52Example 335-(2-Fluorophenyl)-1H-pyrrole-3-carbonitrile (100 g, 537.08 mmole), 4- dimethylaminopyridine (9.84g, 80.56mmole), Diisopropylethylamine (97.18g, 751.81mmole), Acetonitrile (600ml)Add to a three-necked flask (3000 ml), Stir and dissolve at 10-20 C, Then a solution of pyridine-3-sulfonyl chloride (114.47 g, 644.5 mmole) in acetonitrile (200 ml) was added dropwise.Control the internal temperature of the reaction solution does not exceed 30 C, After the addition is completed, Stir at this temperature for 3 hours.Then add 1N hydrochloric acid to adjust the pH value 4-5, Then add 1200ml of water, Mechanical stirring and crystallization, Filtered and dried solid.Add the solid to 1000 ml of acetonitrile. Heated at 60-70 C, Add decolorization with activated carbon, Filter and mechanically stir the filtrate.Add 1000ml of water dropwise, Stirring at room temperature, Filtered, solid at 50 C to dry light yellow products5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole 3-carbonitrile160.86g (yield 91.5%), HPLC purity is greater than 99%.In 500m reaction flask, 200ml of acetonitrile was added, 5- (2-fluorophenyl) -1H-pyrrole-3-carbonitrile (50 g, 0.27 mol), N, N-diisopropylethylamine (41.6 g 0.32 mol) and4-N, N-dimethylaminopyridine (4.69 g, 38.4 mmol), Stir at room temperature. The temperature of the reaction solution was controlled to be not higher than 30 C, and a mixed solution of 3-pyridinesulfonyl chloride (52.5 g, 0.29 mol) in 100 ml of acetonitrile was added dropwise.Dropping completed, 25 C for 2 hours, the reaction is completed, 300ml of purified water was added to the reaction solution, the reaction temperature was controlled not higher than 30 C, the dropwise addition of concentrated hydrochloric acid to adjust the pH to 4-5, 25 C with stirring 2 hours, filtered, washed with a mixture of acetonitrile and water, and the solid was collected and dried under reduced pressure at 50 C to give 79.5 g of 5- (2-fluorophenyl) -1- (pyridin-3-ylsulfonyl) 3-Nitrile yield 90 ' 5%.Example 33 (2)

Molecular Weight:186.18
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:186.05932639
Monoisotopic Mass:186.05932639
Topological Polar Surface Area:39.6
Heavy Atom Count:14
Complexity:245
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes