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With peracetic acid; 4-tolyl iodide; platinum on carbon; at 20℃; for 12h;
General procedure: Amide 1 (0.2 mmol), Pt/SiO2 (loading 1 mol%), 4-Me-C6H4I (0.2 equiv.), AcOOH (2 equiv.), and ROH (1 mL) were added into a reaction tube. The mixture was then stirred for 12 h at room temperature. After the conversion was completed, the catalyst was filtered off and the filtrate was poured into water (5 mL), extracted with EtOAc (5 mL x 3), and dried with Na2SO4, and the solvent was removed under reduced pressure. Product 2 was purified by flash column chromatography using PE/EtOAc as an eluent.
With N-iodo-succinimide; [bis(acetoxy)iodo]benzene; copper(l) chloride In N,N-dimethyl-formamide at 60℃; for 3h;
21
Add N-(3-chlorophenyl)pyridineamide (46.41 mg, 0.2 mmol) and chlorosuccinimide (77.99 mg, 0.6 mmol) into a 25 mL single-neck bottle, copper chloride (5.31 mg, 20 mol%), iodobenzene acetate (128.79 mg, 2.0 eq), N,N-dimethylformamide (4 mL). Stir at 60 °C for 3.0h in an air atmosphere. The mixture was then cooled to room temperature, cooled, filtered, and concentrated under reduced pressure. Purified by silica gel column chromatography (developing solvent: petroleum ether: ethyl acetate = 80:1), 25.00 mg of the white solid target product was obtained with a yield of 47%.
With N-Bromosuccinimide; [bis(acetoxy)iodo]benzene; copper(I) bromide In N,N-dimethyl-formamide at 60℃; for 3h;
22
Add N-(3-chlorophenyl)pyridine amide (46.41 mg, 0.2 mmol) and bromosuccinimide (83.49 mg, 0.48 mmol) into a 25 mL single-necked flask, copper bromide (8.83 mg, 20 mol%), iodobenzene acetate (128.79 g, 2.0 eq), N,N-dimethylformamide (4 mL).Stir at 60°C for 3.0h in an air atmosphere. The mixture was then cooled to room temperature, cooled, filtered, and concentrated under reduced pressure.Purified by silica gel column chromatography (developing solvent: petroleum ether: ethyl acetate = 80:1), 53.31 mg of the white solid target product was obtained with a yield of 86%.
Stage #1: V(647)U0370 With Benzophenone imine; copper(l) chloride In toluene at 80℃; for 16h; Sealed tube;
Stage #2: With hydrogenchloride In tetrahydrofuran; water at 30℃;
General procedure for the copper-catalyzed directed ortho C-H amination of anilines
General procedure: A solution of 2-picolinamide 1a-1z (0.1 mmol, 1.0 eq.) and CuCl (0.15 mmol, 1.5 eq.) in dry toluene (3 mL) was added benzophenone imine (0.25 mmol, 2.5 eq.) in 10 ml sealed vials under air. The mixture was stirred at 80 °C in oil bath for 16 hours. Then the mixture was diluted with EA (20 mL) and washed twice with aqueous solution of ammonia (10 mL), followed by brine (10 mL). The organic phase was evaporated, then diluted with 2 N HCl : THF 1:1 (4 mL) and stirring under 30 °C for 3-12 hours. Saturated NaHCO3 was added and then the mixture was extract with EA three times. The organic phase was washed with brine and dried over anhydrous Na2SO4. Then the organic solvent was evaporated under reduced pressure to give the crude product, which was further purified by flash column chromatography to afford 3a-3z
With triethylamine In dichloromethane at 0 - 20℃; for 3h;
General procedure for the preparation of substrates 1a-1z
General procedure: To a 50 mL round bottom flask was charged with pyridine-2-carboxylic acid (369 mg, 3.0 mmol), then 20 mL DCM was added. The mixture was stirred at 0 °C and then oxalyl chloride (0.5 ml, 6.0 mmol) was added dropwise. Afterwards, 4-5 drops of DMF was added and the mixture was allowed to warm to room temperature. After stirring for 4 hours, the DCM and excess oxalyl chloride was removed under vacuum to obtain crude acyl chloride. Then the crude acyl chloride was dissolved in 20 mL DCM and cooled to 0 °C, Et3N (0.7 mL, 5.0 mmol) and aniline (2.4 mmol) was added, and then the mixture was allowed to warm to room temperature. After 3 hours, 20 mL of water was added to quench the reaction, and organic phase was separated. The aqueous phase was extract twice with 20 mL DCM. Organic phase was combined, and washed with 1 N HCl, saturated NaHCO3, and brine. Then the organic phase was dried over anhydrous Na2SO4, evaporated under reduced pressure. The crude product was purified by flash column chromatography to afford the 2-picolinamide.
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