2-aminoethanol;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A sample of lime was slaked in a solution of ethanolamine chloride, and the resultant suspension was passed through a mesh screen to remove solid matter. The solution of ethanolamine chloride was prepared by mixing ethanolamine with concentrated hydrochloric acid, to give a 1:1.6 solution of ethanolamine hydrochloride in water. The resultant lime/ethanolamine chloride solution was treated with carbon dioxide to form precipitated calcium carbonate. to remove solid matter

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethanolamine chloride was prepared by mixing 2207 grams of ethanolamine with 3819 grams of concentrated hydrochloric acid, to give a 1:2 solution of ethanolamine hydrochloride in water, 1125 grams of the lime of Example 1 were added to the solution, which was then stirred for a period of one hour. The solution was brown in colour.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethanolamine (2-aminoethanol) (98%, 1.750 kg, 28.0 moles) in isopropanol (7.0 l) was stirred to yield a homogeneous solution. Thereto triphenylchloromethane (97%, 2.020 kg, 7.03 moles) was added slowly within 1 h at room temperature with stirring, whereat the temperature was not to exceed 30° C. After completed dissolution of triphenylchloromethane (whereat ethanolamine hydrochloride separated as a white precipitate) the reaction mixture was stirred for another hour and cooled to room temperature. The precipitate, which separated, was filtered off and the filtrate was poured into ice-cold water (8.0 l). The precipitate, which separated, was filtered off and dried in vacuo at a temperature not exceeding 50° C. Thus there were obtained 2.120 kg (98%) of the desired compound. to yield a homogeneous solution with stirring, whereat the temperature to exceed 30° C separated as a white precipitate) the reaction mixture was stirred for another hour The precipitate, which separated was filtered off the filtrate was poured into ice-cold water (8.0 l) The precipitate, which separated was filtered off dried in vacuo at a temperature not exceeding 50° C

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethanolamine (2-aminoethanol) (98%, 1.750 kg, 28.0 moles) in isopropanol (7.0 l) was stirred to yield a homogeneous solution. Thereto triphenylchloromethane (97%, 2.020 kg, 7.03 moles) was added slowly within 1 h at room temperature with stirring, whereat the temperature was not to exceed 30° C. After completed dissolution of triphenylchloromethane (whereat ethanolamine hydrochloride separated as a white precipitate) the reaction mixture was stirred for another hour and cooled to room temperature. The precipitate, which separated, was filtered off and the filtrate was poured into ice-cold water (8.0 l). The precipitate, which separated, was filtered off and dried in vacuo at a temperature not exceeding 50° C. Thus there were obtained 2.120 kg (98%) of the desired compound. to yield a homogeneous solution with stirring, whereat the temperature to exceed 30° C separated as a white precipitate) the reaction mixture was stirred for another hour The precipitate, which separated was filtered off the filtrate was poured into ice-cold water (8.0 l) The precipitate, which separated was filtered off dried in vacuo at a temperature not exceeding 50° C

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The reaction between monoethanolamine hydrochloride and thionylchloride is carried out in a molar ratio of 1:1.05 - 1.2, at 50° to 100°C. for 3 to 10 hours, in water-insoluble solvents such as benzene, toluene, xylene, monochlorobenzene, dichlorobenzene and 1,2-dichloroethane, and in the presence of a catalyst such as dimethylformamide, diethylformamide, N-methylpyrrolidone and pyridine to obtain 2-chloroethylamine hydrochloride with good purity. And, as a result of further investigation, the inventors have found that sulfur dioxide which is produced as a by-product in the course of the chlorination acts as a negative catalyst in the subsequent amidation, i.e. the reaction between the sulfonylhalide (II) and the resulting 2-chloroethyl-amine or salts thereof, and that the yield can be much increased by forcing sulfur dioxide to be removed.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 0.5 g, 1.264 mmol), 2-aminoethanol hydrochloride (0.123 g, 1.896 mmol), iPrOH (4 mL) and DIPEA (0.442 mL, 0.327 g, 2.53 mmol) were subjected to MW irradiation at 140° C. for 2 h. The vial was cooled to RT and the RM was poured into water (100 mL) and the resulting precipitate was collected by filtration. The obtained solid was washed with water (50 mL) and dried to afford the title compound without further purification. LC-MS (Condition 6) tR=1.14 min, m/z=419.8 [M+H]+. were subjected to MW irradiation at 140° C. for 2 h the resulting precipitate was collected by filtration The obtained solid was washed with water (50 mL) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 0.5 g, 1.264 mmol), 2-aminoethanol hydrochloride (0.123 g, 1.896 mmol), iPrOH (4 mL) and DIPEA (0.442 mL, 0.327 g, 2.53 mmol) were subjected to MW irradiation at 140° C. for 2 h. The vial was cooled to RT and the RM was poured into water (100 mL) and the resulting precipitate was collected by filtration. The obtained solid was washed with water (50 mL) and dried to afford the title compound without further purification. LC-MS (Condition 6) tR=1.14 min, m/z=419.8 [M+H]+. were subjected to MW irradiation at 140° C. for 2 h the resulting precipitate was collected by filtration The obtained solid was washed with water (50 mL) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethanolamine hydrochloride (9.9 g; 100 mmol) is partially dissolved in CH2Cl2 /CH3CN (200 ml/100 ml) and Et3N (23 ml; 170 mmol) is then added. Tritylchloride (18.9 g; 67.6 mmol) is added portionwise over 30 minutes. After the addition is complete the reaction mixture is allowed to stir an additional 30 minutes, diluted with CH2Cl2, washed With H2O 2× and brine, dried (MgSO4), concentrated in vacuo and purified by column chromatography with silica/CH2Cl2 to give N-tritylethanolamine as an oil which is used directly in Step B. After the addition washed With H2O 2× and brine dried (MgSO4) concentrated in vacuo purified by column chromatography with silica/CH2Cl2

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethanolamine hydrochloride (9.9 g; 100 mmol) is partially dissolved in CH2Cl2 /CH3CN (200 ml/100 ml) and Et3N (23 ml; 170 mmol) is then added. Tritylchloride (18.9 g; 67.6 mmol) is added portionwise over 30 minutes. After the addition is complete the reaction mixture is allowed to stir an additional 30 minutes, diluted with CH2Cl2, washed With H2O 2× and brine, dried (MgSO4), concentrated in vacuo and purified by column chromatography with silica/CH2Cl2 to give N-tritylethanolamine as an oil which is used directly in Step B. After the addition washed With H2O 2× and brine dried (MgSO4) concentrated in vacuo purified by column chromatography with silica/CH2Cl2

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A sample of lime was slaked in a solution of ethanolamine chloride, and the resultant suspension was passed through a mesh screen to remove solid matter. The solution of ethanolamine chloride was prepared by mixing ethanolamine with concentrated hydrochloric acid, to give a 1:1.6 solution of ethanolamine hydrochloride in water. The resultant lime/ethanolamine chloride solution was treated with carbon dioxide to form precipitated calcium carbonate. to remove solid matter

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethanolamine chloride was prepared by mixing 2207 grams of ethanolamine with 3819 grams of concentrated hydrochloric acid, to give a 1:2 solution of ethanolamine hydrochloride in water, 1125 grams of the lime of Example 1 were added to the solution, which was then stirred for a period of one hour. The solution was brown in colour.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethanolamine (2-aminoethanol) (98%, 1.750 kg, 28.0 moles) in isopropanol (7.0 l) was stirred to yield a homogeneous solution. Thereto triphenylchloromethane (97%, 2.020 kg, 7.03 moles) was added slowly within 1 h at room temperature with stirring, whereat the temperature was not to exceed 30° C. After completed dissolution of triphenylchloromethane (whereat ethanolamine hydrochloride separated as a white precipitate) the reaction mixture was stirred for another hour and cooled to room temperature. The precipitate, which separated, was filtered off and the filtrate was poured into ice-cold water (8.0 l). The precipitate, which separated, was filtered off and dried in vacuo at a temperature not exceeding 50° C. Thus there were obtained 2.120 kg (98%) of the desired compound. to yield a homogeneous solution with stirring, whereat the temperature to exceed 30° C separated as a white precipitate) the reaction mixture was stirred for another hour The precipitate, which separated was filtered off the filtrate was poured into ice-cold water (8.0 l) The precipitate, which separated was filtered off dried in vacuo at a temperature not exceeding 50° C