拉莫三嗪杂质16

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:36.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 163 g 2,3-Dichloroaniline (1.0 mol) is added to a mixture of 3250 g of 30% aqueous HBr (12.0 mole) and 25.4 g copper powder of a particle size of approx. 45μ at 35-37° C. The mixture is stirred for 15 minutes at 35-37° C. Then, 766 g of an aqueous solution of NaNO2 (40% solution in water, 4.44 mole) is added via subsurface feeding over a period of 3 hours at 35° C. Parallel to the addition of the sodium nitrite 489 g 2,3-dichloroaniline (3.0 mol) is added over a period of 2.5 hours at the same temperature. The addition of dichloraniline starts 15 minutes after the start of the addition of sodium nitrite. After all additions are complete the reaction mixture is stirred for 30 minutes at 35° C. Then, the reaction mixture is heated to 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase. The remaining liquid is discarded and the crude product is washed twice with 200 ml water. 792.2 g of crude solid 1-bromo-2,3-dichlorobenzene is obtained (87.7% of theory) with a purity of 86.2%). feeding over a period of 3 hours at 35° C is added over a period of 2.5 hours at the same temperature starts 15 minutes is stirred for 30 minutes at 35° C Then, the reaction mixture is heated to 60-65° C The organic phase containing the reaction product is separated from the aqueous phase the crude product is washed twice with 200 ml water

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 32.7 g 2,3-Dichloroaniline (0.20 mole) is added to a mixture of 21.4 g of NaBr (0.20 mole, 1.0 equivalent), 110.0 g of 48% aqueous HBr (0.66 mole, 3.3 equivalents) and 70 ml water at 30-40° C. The mixture is stirred for 15 minutes at 30-40° C. and then heated to 45° C. Then 5.1 g CuSO4*5H2O (0.02 mole, 0.10 equivalent) is added and the mixture is stirred for 15 minutes at 45° C. After this, an aqueous solution of NaNO2 (40% solution in water, 37.6 g, 0.22 mole, 1.1 equivalents) is added via subsurface feeding over a period of 2 hours at 45° C. The reaction mixture is stirred for 30 minutes at 45° C. After this, the reaction mixture is heated to 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase and is cooled to ambient temperature, leading to solidification of the reaction product. The remaining liquid is discarded and the crude product is washed twice with 10 ml water and dried under vacuum. 44.0 g (83% of theory) of 1-bromo-2,3-dichlorobenzene is obtained in the form of a light brown solid (purity: 85%). heated to 45° C the mixture is stirred for 15 minutes at 45° C feeding over a period of 2 hours at 45° C The reaction mixture is stirred for 30 minutes at 45° C After this, the reaction mixture is heated to 60-65° C The organic phase containing the reaction product is separated from the aqueous phase is cooled to ambient temperature the crude product is washed twice with 10 ml water dried under vacuum

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 32.7 g 2,3-Dichloroaniline (0.20 mole) is added to a mixture of 168.5 g of 48% aqueous HBr (1.0 mole, 5.0 equivalents) and 40 ml water at 30-40° C. The mixture is stirred for 15 minutes at 30-40° C. and then heated to 45° C. Then 2.9 g Cu(I)Br (0.02 mole, 0.10 equivalent) is added and the mixture is stirred for 15 minutes at 45° C. After this, an aqueous solution of NaNO2 (40% solution in water, 35.6 g, 0.21 mole, 1.0 equivalents) is added via subsurface feeding over a period of 2 hours at 45° C. The reaction mixture is stirred for 30 minutes at 45° C. After this, the reaction mixture is heated to 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase and is cooled to ambient temperature, leading to solidification of the reaction product. The remaining liquid is discarded and the crude product is washed twice with 10 ml water and dried under vacuum. 40.0 g (80% of theory) of 1-bromo-2,3-dichlorobenzene is obtained in the form of a light brown solid (purity: 90%). heated to 45° C the mixture is stirred for 15 minutes at 45° C feeding over a period of 2 hours at 45° C The reaction mixture is stirred for 30 minutes at 45° C After this, the reaction mixture is heated to 60-65° C The organic phase containing the reaction product is separated from the aqueous phase is cooled to ambient temperature the crude product is washed twice with 10 ml water dried under vacuum

反应条件: temp:37.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 32.7 g 2,3-Dichloroaniline (0.20 mole) is added to a mixture of 21.4 g of NaBr (0.20 mole, 1.0 equivalent), 110.0 g of 48% aqueous HBr (0.66 mole, 3.3 equivalents) and 70 ml water at 30-45° C. The mixture is stirred for 15 minutes at 30-45° C. and then heated to 60° C. Then 2.9 g Cu(I)Br (0.02 mole, 0.10 equivalent) is added and the mixture is stirred for 15 minutes at 60° C. After this, an aqueous solution of NaNO2 (40% solution in water, 37.6 g, 0.22 mole, 1.1 equivalents) is added via subsurface feeding over a period of 2 hours at 60-65° C. The reaction mixture is stirred for 30 minutes at 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase and is cooled to ambient temperature, leading to solidification of the reaction product. The remaining liquid is discarded and the crude product is washed two times with 10 ml water and dried under vacuum. 44.0 g (89% of theory) of 1-bromo-2,3-dichlorobenzene is obtained in the form of a light brown solid (purity: 91%). For further characterisation, the crude product was purified by vacuum distillation (130° C./20 mmHg). 38.0 g (84% of theory) of pure 1-bromo-2,3-dichlorobenzene is obtained in the form of white crystals. heated to 60° C the mixture is stirred for 15 minutes at 60° C feeding over a period of 2 hours at 60-65° C The reaction mixture is stirred for 30 minutes at 60-65° C The organic phase containing the reaction product is separated from the aqueous phase is cooled to ambient temperature the crude product is washed two times with 10 ml water dried under vacuum

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

实验步骤: Dimethylaminopyridine (50 mg) and dimethylaminopropylethylcarbodiimide hydrochloride (0.5 g) were added to a solution of 2-(1-ethyl-5-phenylimidazolidin-4-on-3-yl)isobutyric acid (0.6 g) prepared according to Example 8 in dichloromethane (15 mL) at 0° C. After stirring for 15 minutes at 0° C. to room temperature, 2,3-dichioroaniline (0.4 g) was added and the mixture was stirred overnight at room temperature. The reaction solution was poured into water whose pH was 2, and the mixture was extracted with chloroform. The organic layer was washed with water and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the resulting crude product was purified by thin-layer chromatography (silica gel, ethyl acetate/n-hexane=2/3) to give 0.2 g of the title compound. prepared the mixture was stirred overnight at room temperature the mixture was extracted with chloroform The organic layer was washed with water dried over anhydrous sodium sulfate After distilling off the solvent under reduced pressure the resulting crude product was purified by thin-layer chromatography (silica gel, ethyl acetate/n-hexane=2/3)