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

In a four-necked flask, 5-(2-fluorophenyl)-1H-pyrrole-3-carbonitrile (10.0 g, 53.71 mmol) and THF (30 mL) were added and dissolved, and acetic acid (50 mL) and water (10 mL) were added. Example 3Compound (4) (6.62g, 35.6mmol), tetrahydrofuran (45ml), formic acid (36.5 ml), water (15ml), and Raney nickel (397.2um, wet weight 5.3g) was added to the reaction flask. In a hydrogen atmosphere (0.1 MPa) and room humidity, the reaction was stirred for 2.5 hours. After the reaction was complete, the system was purged with nitrogen, the solution was filtered and washed with ethyl acetate (25 ml x 2). The filtrate was adjusted to pH 6 to 7 with 5N aqueous sodium hydroxide under ice-cooling. After phase separation, the ethyl acetate layer was collected and the aqueous layer was extracted again with ethyl acetate (25 ml). The ethyl acetate layers were combined, washed sequentially with saturated aqueous sodium bicarbonate and saturated brine, dissolved in ethyl acetate (20 ml), stirred on 100 to 200 mesh silica gel and spin dried. The resulting solution was purified by silica gel column chromatography (mobile phase: petroleum ether: ethyl acetate = 5: 1 to 3: 1) and dried under reduced pressure to give a pale yellow solid (3.47 g, yield 51.5percent).1 g of the intermediate V-1 was dissolved in a mixed solution of 20 ml of tetrahydrofuran, 6 ml of acetic acid and 1 ml of water, then 1 ml of Raney nickel was added, hydrogen gas was introduced, and the reaction was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, to give a compound of Formula VI-1, 427 mg of a white solid, yield 42percentSodium bromate was added 52g (0.34mol) in a beaker, 400ml of water and dissolved with stirring, as a backup solution, the other solution of (5- (2-fluorophenyl) lH-pyrrol-3-yl) in a 3000 ml three-necked flask - methanol (6) 191g (1.0mol), dichloromethane 400ml, n-butanol 400ml, 35percent sulfuric acid 20g (0.07mol), sodium bromide 1.2g, ice-salt bath to 0 ~ 5 , bromine was added dropwise sodium stock solution, an ice-salt bath after the addition stirring was continued for 3.5h, TLC detection starting material the reaction is completed, the reaction solution was transferred to a single neck flask, under reduced pressure to remove most of the organic solvent was concentrated under rotation, the precipitated yellow solid was cooled in a water bath with stirring 0.5h, yellow solid was collected by filtration, dried under reduced pressure to give 5- (2-fluorophenyl) lH-pyrrole-3-carbaldehyde 180g, (HPLC content: 98.4percent), yield 95.1percent.In 2000ml reaction flask was added Compound VII 100g, was added methylene chloride 800ml, iodine 177g, stirred at room temperature for 12h, the reaction was completed, filtered through celite, diatomaceous earth leached with 60ml of dichloromethane, The dichloromethane was concentrated to dryness, 400ml isopropanol was added, stirred overnight, a solid precipitated, cooled to 0 ~ 10 °C, incubated for 1h, suction filtered to give a brown solid 91 g, namely 5- (2-fluorophenyl ) -1H-pyrrole-3-carbaldehyde in 92percent yield and 99.2percent purity.Reference Example 17 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde; A solution (220 mL) of ethyl 5-(2-fluorophenyl)-1H-pyrrole-3-carboxylate (11.6 g) in tetrahydrofuran was cooled to -78° C., and a 1.5 mol/L solution (100 mL) of diisobutylaluminum hydride in toluene was added dropwise over 10 min. The mixture was stirred at -78° C. for 1 hr and water (10 mL) was added dropwise over 2 min. The mixture was allowed to warm to room temperature and the mixture was stirred for 2 hr. The reaction mixture was filtered by adding celite and anhydrous magnesium sulfate and concentrated under reduced pressure to give a pale-yellow oil (yield 8.3 g). To a solution (220 mL) of the obtained pale-yellow oil (8.30 g) in acetonitrile were added tetra-n-propylammonium perruthenate (1.75 g), N-methylmorpholine N-oxide (13.5 g) and molecular sieves 4A powder (5 g), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3-->1:1) to give the title compound as yellow crystals (yield 5.6 g, 60percent). Reference Example 111 Diisobutyl aluminum hydride 2.4ml dissolved in toluene, placed at -78 , take 2.3g dissolved in 100ml of tetrahydrofuranWas added dropwise to the reactor. After stirring for 1 hour, 2 ml of water was added slowly, and the mixture was stirred at room temperature for 1 hour.Adding anhydrous magnesium sulfate, filtering and concentrating the filtrate to dryness, dissolving in 45ml of acetonitrile, adding 2.36g of NMO, 0.46g TPAP, molecular sieves, reaction at room temperature for 1.5 hours, the filtrate filtered diatomite, vacuum concentration, eluentWith hexane: ethyl acetate = 4: 1-1: 1 over the column that 1.1g, 60percent yield.Dimethyl sulfoxide (200 mL) was added to a 500 mL three-neck flask, and 2-fluorobenzoic acid (II) (14.2 g, 0.1 mol) was added under nitrogen.5-bromopyrrole-3-carbaldehyde (III) (35.5 g, 0.2 mol), sodium hydroxide (40.1 g, 1 mol), Pd(PPh3)2Cl2 (14.1 g, 0.02 mol), CuOAc (4.9 g, 0.04 mol) , 1, 10-Phenanthroline (7.3g, 0.04mol), stirring, heating to 140°C, reaction for 5h, The reaction was completed by HPLC (2-fluorobenzoic acid (II) content is less than 1percent), the temperature was lowered to 20°C, the pH was adjusted to 6 with 5percent aqueous hydrochloric acid solution, and the solid was slowly precipitated by adding water.The solid was extracted with ethyl acetate (50 mL X 3).The resulting organic phase was washed with saturated sodium bicarbonate solution (100 mL) and saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to 80 g and re-crystallized by the dropwise addition of petroleum ether (150 mL).Filtration drying gave a reddish solid product (18.5 g, yield: 96.5percent based on 2-fluorobenzoic acid (II)).Weigh 15.0 g (0.086 mol) of 5-bromopyrrole-3-carbaldehyde, 19.0 g (0.136 mol) of 2-fluorophenylboronic acid, 15.0 g of potassium carbonate in a four-necked flask, and add 100 g of DMF and 40 g of water in a nitrogen atmosphere. A catalytic amount of tetrakis(triphenylphosphine)palladium was added thereto, and the temperature was raised to 105 ° C, and the reaction was carried out for 20 hours. After the reaction was completed, the temperature was lowered to room temperature, diluted with water, and extracted with ethyl acetate. The extract was dried, suction filtered, concentrated and weighed. Crystallization gave 13.5 g of gray solid 1, yield 82.8percent, purity 99.94percentExample 52

Molecular Weight:189.19
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:189.058992041
Monoisotopic Mass:189.058992041
Topological Polar Surface Area:32.9
Heavy Atom Count:14
Complexity:210
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes