卢非酰胺杂质

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 16.9 g (0.1 mole) of 2,6-difluorobenzyl azide and 8.3 g (0.1 mole) of but-2-ynecarboxamide are heated in 20 ml of dioxane for 16 hours to 100° C. After removing the dioxane by evaporation, the desired isomer is separated by column chromatography, to give 1-(2,6-difluorobenzyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide with a melting point of 208°-210° C. (recrystallisation from methanol). After removing the dioxane by evaporation the desired isomer is separated by column chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The starting material is prepared as follows: 2.53 g (0.11 mole) of sodium are dissolved in 60 ml of alcohol, then a mixture of 16.9 g (0.1 mole) of 2,6-difluorobenzyl azide and 14,3 g (0.11 mole) of ethyl acetoacetat in 60 ml of alcohol is added and the batch is heated for 16 hours to reflux. After addition of 120 ml of normal sodium hydroxide solution, the reaction mixture is refluxed for another 2 hours, then diluted with 200 ml of water and acidified to pH 1 with hydrochloric acid while cooling. The precipitated product is filtered with suction, washed first with water and then with ether and dried, affording 1-(2,6-difluorobenzyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid with a melting point of 166°-167° C. The starting material is prepared is added the batch is heated for 16 hours to reflux the reaction mixture is refluxed for another 2 hours while cooling The precipitated product is filtered with suction washed first with water with ether and dried

反应条件: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 0.200 g (1.23 mmol) of 2,6-difluorobenzyl chloride in 0.5 mL of DMSO was added dropwise to a mixture of 0.090 g (1.23 mmol) of NaN3 in 2 mL of DMSO at 20-25° C. The reaction was left stirring at 20-25° C. during 4 h. until showing completion by TLC. The crude was treated with 1.6 mL of water and 1.6 mL of cyclohexane and the organic phase was vacuum distilled to obtain 0.210 g (97%) of 2,6-difluorobenzyl azide as yellowish oil The reaction was left distilled

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorobenzyl azide (34.2 g), 2-chloroacrylonitrile (17.73 g) and water. (125 ml) is stirred for 24 hours at about 80° C. By increasing the external temperature to about 130° C., excess 2-chloroacrylonitrile is distilled off. The semisolid mixture is cooled to about 40° C., cyclohexane (50 ml) is added to the suspension and the mixture is brought to about 20° C. and stirred for about 2 hours. The product is isolated by filtration and washed with cyclohexane (75 ml) and then with water (50 ml). The moist product is mixed with water (100 ml), the suspension is filtered and the product is washed with water (50 ml) and dried at about 60° C. in vacuo. Yield: 38.04 g=86%. By increasing the external temperature to about 130° C. excess 2-chloroacrylonitrile is distilled off The semisolid mixture is cooled to about 40° C. cyclohexane (50 ml) is added to the suspension is brought to about 20° C. stirred for about 2 hours The product is isolated by filtration washed with cyclohexane (75 ml) The moist product is mixed with water (100 ml) the suspension is filtered the product is washed with water (50 ml) dried at about 60° C. in vacuo

反应条件: temp:82.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorobenzylazide (9,22 g), 2-chloroacryonitrile (6,68 g) and water is stirred at about 82° C. for about 24 hours. 2-Chloroacrylnitrile is distilled off by raising the external temperature to about 113° C. excess. The mixture is cooled to about 40° C. and toluene (10 ml) is added. Within about 40 minutes at about 80° C. sodium hydroxide (5,5 ml—30%) is added the amide being crystallized. By raising the external temperature to 112° C., toluene is distilled off. The suspension is cooled to 20° C. and the product is isolated by filtration, washed with water (200 ml) and dried at about 60° C. in vacuo. 2-Chloroacrylnitrile is distilled off by raising the external temperature to about 113° C. excess The mixture is cooled to about 40° C. toluene (10 ml) is added Within about 40 minutes at about 80° C. sodium hydroxide (5,5 ml—30%) is added the amide being crystallized By raising the external temperature to 112° C. toluene is distilled off The suspension is cooled to 20° C. the product is isolated by filtration washed with water (200 ml) dried at about 60° C. in vacuo

反应条件: temp:82.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorobenzylazide (9,22 g), 2-chloroacryonitrile (6,68 g) and water is stirred at about 82° C. for about 24 hours. 2-Chloroacrylnitrile is distilled off by raising the external temperature to about 113° C. excess. The mixture is cooled to about 40° C. and toluene (10 ml) is added. Within about 40 minutes at about 80° C. sodium hydroxide (5,5 ml—30%) is added the amide being crystallized. By raising the external temperature to 112° C., toluene is distilled off. The suspension is cooled to 20° C. and the product is isolated by filtration, washed with water (200 ml) and dried at about 60° C. in vacuo. 2-Chloroacrylnitrile is distilled off by raising the external temperature to about 113° C. excess The mixture is cooled to about 40° C. toluene (10 ml) is added Within about 40 minutes at about 80° C. sodium hydroxide (5,5 ml—30%) is added the amide being crystallized By raising the external temperature to 112° C. toluene is distilled off The suspension is cooled to 20° C. the product is isolated by filtration washed with water (200 ml) dried at about 60° C. in vacuo

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorbenzyl azide (34.2 g), 2-chloroacrylonitrile (26.6 g) and N,N-dimethylformamide (125 ml) is stirred at about 80° C. for 24 hours. Unreacted 2-chloroacrylonitrile and 2,6-difluorobenzyl azide as well as N,N-dimethylformamide are distilled off (distillate 100 ml) by raising the external temperature to about 130° C. and gradually evacuating to about 100 mbar. After cooling to 100° C., water (100 ml) is allowed to run in. The crystallization of the product is initiated by seeding the brown emulsion. The mixture is cooled to about 20° C. and the suspension is stirred at about 20° C. for 30 minutes. The product is isolated by filtration and washed with water (100 ml). The product is dried in vacuo at about 60° C. Yield: 34.40 g=78.1% (beige crystals). are distilled off (distillate 100 ml) by raising the external temperature to about 130° C. gradually evacuating to about 100 mbar After cooling to 100° C. The crystallization of the product The mixture is cooled to about 20° C. the suspension is stirred at about 20° C. for 30 minutes The product is isolated by filtration washed with water (100 ml) The product is dried in vacuo at about 60° C

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorbenzyl azide (34.2 g), 2-chloroacrylonitrile (26.6 g) and N,N-dimethylformamide (125 ml) is stirred at about 80° C. for 24 hours. Unreacted 2-chloroacrylonitrile and 2,6-difluorobenzyl azide as well as N,N-dimethylformamide are distilled off (distillate 100 ml) by raising the external temperature to about 130° C. and gradually evacuating to about 100 mbar. After cooling to 100° C., water (100 ml) is allowed to run in. The crystallization of the product is initiated by seeding the brown emulsion. The mixture is cooled to about 20° C. and the suspension is stirred at about 20° C. for 30 minutes. The product is isolated by filtration and washed with water (100 ml). The product is dried in vacuo at about 60° C. Yield: 34.40 g=78.1% (beige crystals). are distilled off (distillate 100 ml) by raising the external temperature to about 130° C. gradually evacuating to about 100 mbar After cooling to 100° C. The crystallization of the product The mixture is cooled to about 20° C. the suspension is stirred at about 20° C. for 30 minutes The product is isolated by filtration washed with water (100 ml) The product is dried in vacuo at about 60° C

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorobenzyl azide (34.2 g), 2-chloroacrylonitrile (26.6 g) and toluene (125 ml) is stirred at about 80° C. for 24 hours. Unreacted 2-chloroacrylonitrile and 2,6-difluorobenzyl azide as well as toluene are distilled off (distillate 100 ml) by raising the external temperature to about 130° C. After cooling to 80° C., n-heptane (100 ml) is allowed to run in. The mixture is cooled to about 20° C. and the suspension is stirred at about 20° C. for 1 hour. The product is isolated by filtration and washed with n-heptane (100 ml). The product is dried in vacuo at about 60° C. Yield: 22.31 g=50.7% (beige powder). are distilled off (distillate 100 ml) by raising the external temperature to about 130° C After cooling to 80° C. The mixture is cooled to about 20° C. the suspension is stirred at about 20° C. for 1 hour The product is isolated by filtration washed with n-heptane (100 ml) The product is dried in vacuo at about 60° C

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorobenzyl azide (34.2 g), 2-chloroacrylonitrile (26.6 g) and n-heptane (125 ml) is stirred at about 80° C. for 24 hours, whereby a suspension results. Unreacted 2-chloroacrylonitrile and 2,6-difluorobenzyl azide as well as n-heptane are distilled off (distillate 25 ml) by raising the external temperature to about 130° C. The mixture is cooled to about 20° C. and the suspension is stirred at about 20° C. for about 2 hours. The product is isolated by filtration, washed with n-heptane (100 ml) and dried in vacuo at about 60° C. Yield: 20.45 g=46.4% (beige powder). whereby a suspension results are distilled off (distillate 25 ml) by raising the external temperature to about 130° C The mixture is cooled to about 20° C. the suspension is stirred at about 20° C. for about 2 hours The product is isolated by filtration washed with n-heptane (100 ml) dried in vacuo at about 60° C

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,6-difluorobenzyl azide (34.2 g), 2-chloroacrylonitrile (26.6 g) and n-heptane (125 ml) is stirred at about 80° C. for 24 hours, whereby a suspension results. Unreacted 2-chloroacrylonitrile and 2,6-difluorobenzyl azide as well as n-heptane are distilled off (distillate 25 ml) by raising the external temperature to about 130° C. The mixture is cooled to about 20° C. and the suspension is stirred at about 20° C. for about 2 hours. The product is isolated by filtration, washed with n-heptane (100 ml) and dried in vacuo at about 60° C. Yield: 20.45 g=46.4% (beige powder). whereby a suspension results are distilled off (distillate 25 ml) by raising the external temperature to about 130° C The mixture is cooled to about 20° C. the suspension is stirred at about 20° C. for about 2 hours The product is isolated by filtration washed with n-heptane (100 ml) dried in vacuo at about 60° C