2,6-dichloro-N-trimethylsilylaniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution consisting of 102.4 mg (0.415 mmole) of 2-chlorosulfonyl-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine, 2.0 ml of acetonitrile, and 33.6 μl (0.415 mmole) of pyridine was stirred 5 minutes. N-trimethylsilyl-2,6-dichloroaniline, 86.9 μl (0.456 mmole) was added. The solution was stirred at room temperature for 16 hours and the reaction monitored by thin layer chromatography and by reverse phase HPLC. The 2-chlorosulfonyl compound gradually disappeared and a new peak appeared. The reaction was about 10-30 percent complete after 16 hours. An additional 33.6 μl of pyridine was added and the solution heated at 65° C. for 4 hours and at reflux for 16 hours. The solvent was removed under nitrogen and the residue treated with 4 ml of 0.5N NaOH and stirred for 0.5 hour. The solution was extracted with CH2Cl2, acidified with concentrated HCl and filtered. The precipitate was washed with water and dissolved in CH3CN. The resulting solution was heated to reflux, filtered through silica gel and the solvent removed in vacuo to obtain 119 mg (0.321 mmole, 77.2 percent yield) of N-(2,6-dichlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide as a light yellow solid. The product was further purified by washing with acetone, and recrystallizing from refluxing CH3CN to obtain 91.5 mg (0.246 mmole) of product as a white powder, m.p. 263°-265° C. The solution was stirred at room temperature for 16 hours complete after 16 hours at reflux for 16 hours The solvent was removed under nitrogen the residue treated with 4 ml of 0.5N NaOH stirred for 0.5 hour The solution was extracted with CH2Cl2 filtered The precipitate was washed with water dissolved in CH3CN The resulting solution was heated to reflux filtered through silica gel the solvent removed in vacuo

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

実験手順: A solution of 60 ml of benzene, 5.0 g (30.9 mmole) of 2,6-dichloroaniline, 10.6 ml (76.0 mmole) of triethylamine, and 8.08 ml (61.1 mmole) of trimethylsilyl bromide was heated at reflux for 54 hours, cooled, filtered, and the solvent was removed from the filtrate in vacuo. The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide. The residual mixture was filtered into a round-bottomed flask and distilled using a short Vigreaux column to provide 5.43 g (23.2 mmole, 75.0 percent yield) of the N-trimethylsilyl-2,6-dichloroaniline as a 97 percent pure amber oil, bp 74° C.-75° C. at 0.4 mm. at reflux for 54 hours cooled filtered the solvent was removed from the filtrate in vacuo The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide The residual mixture was filtered into a round-bottomed flask distilled

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution consisting of 102.4 mg (0.415 mmole) of 2-chlorosulfonyl-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine, 2.0 ml of acetonitrile, and 33.6 μl (0.415 mmole) of pyridine was stirred 5 minutes. N-trimethylsilyl-2,6-dichloroaniline, 86.9 μl (0.456 mmole) was added. The solution was stirred at room temperature for 16 hours and the reaction monitored by thin layer chromatography and by reverse phase HPLC. The 2-chlorosulfonyl compound gradually disappeared and a new peak appeared. The reaction was about 10-30 percent complete after 16 hours. An additional 33.6 μl of pyridine was added and the solution heated at 65° C. for 4 hours and at reflux for 16 hours. The solvent was removed under nitrogen and the residue treated with 4 ml of 0.5N NaOH and stirred for 0.5 hour. The solution was extracted with CH2Cl2, acidified with concentrated HCl and filtered. The precipitate was washed with water and dissolved in CH3CN. The resulting solution was heated to reflux, filtered through silica gel and the solvent removed in vacuo to obtain 119 mg (0.321 mmole, 77.2 percent yield) of N-(2,6-dichlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide as a light yellow solid. The product was further purified by washing with acetone, and recrystallizing from refluxing CH3CN to obtain 91.5 mg (0.246 mmole) of product as a white powder, m.p. 263°-265° C. The solution was stirred at room temperature for 16 hours complete after 16 hours at reflux for 16 hours The solvent was removed under nitrogen the residue treated with 4 ml of 0.5N NaOH stirred for 0.5 hour The solution was extracted with CH2Cl2 filtered The precipitate was washed with water dissolved in CH3CN The resulting solution was heated to reflux filtered through silica gel the solvent removed in vacuo

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution consisting of 102.4 mg (0.415 mmole) of 2-chlorosulfonyl-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine, 2.0 ml of acetonitrile, and 33.6 μl (0.415 mmole) of pyridine was stirred 5 minutes. N-trimethylsilyl-2,6-dichloroaniline, 86.9 μl (0.456 mmole) was added. The solution was stirred at room temperature for 16 hours and the reaction monitored by thin layer chromatography and by reverse phase HPLC. The 2-chlorosulfonyl compound gradually disappeared and a new peak appeared. The reaction was about 10-30 percent complete after 16 hours. An additional 33.6 μl of pyridine was added and the solution heated at 65° C. for 4 hours and at reflux for 16 hours. The solvent was removed under nitrogen and the residue treated with 4 ml of 0.5N NaOH and stirred for 0.5 hour. The solution was extracted with CH2Cl2, acidified with concentrated HCl and filtered. The precipitate was washed with water and dissolved in CH3CN. The resulting solution was heated to reflux, filtered through silica gel and the solvent removed in vacuo to obtain 119 mg (0.321 mmole, 77.2 percent yield) of N-(2,6-dichlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide as a light yellow solid. The product was further purified by washing with acetone, and recrystallizing from refluxing CH3CN to obtain 91.5 mg (0.246 mmole) of product as a white powder, m.p. 263°-265° C. The solution was stirred at room temperature for 16 hours complete after 16 hours at reflux for 16 hours The solvent was removed under nitrogen the residue treated with 4 ml of 0.5N NaOH stirred for 0.5 hour The solution was extracted with CH2Cl2 filtered The precipitate was washed with water dissolved in CH3CN The resulting solution was heated to reflux filtered through silica gel the solvent removed in vacuo

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

実験手順: A solution of 60 ml of benzene, 5.0 g (30.9 mmole) of 2,6-dichloroaniline, 10.6 ml (76.0 mmole) of triethylamine, and 8.08 ml (61.1 mmole) of trimethylsilyl bromide was heated at reflux for 54 hours, cooled, filtered, and the solvent was removed from the filtrate in vacuo. The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide. The residual mixture was filtered into a round-bottomed flask and distilled using a short Vigreaux column to provide 5.43 g (23.2 mmole, 75.0 percent yield) of the N-trimethylsilyl-2,6-dichloroaniline as a 97 percent pure amber oil, bp 74° C.-75° C. at 0.4 mm. at reflux for 54 hours cooled filtered the solvent was removed from the filtrate in vacuo The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide The residual mixture was filtered into a round-bottomed flask distilled

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution consisting of 102.4 mg (0.415 mmole) of 2-chlorosulfonyl-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine, 2.0 ml of acetonitrile, and 33.6 μl (0.415 mmole) of pyridine was stirred 5 minutes. N-trimethylsilyl-2,6-dichloroaniline, 86.9 μl (0.456 mmole) was added. The solution was stirred at room temperature for 16 hours and the reaction monitored by thin layer chromatography and by reverse phase HPLC. The 2-chlorosulfonyl compound gradually disappeared and a new peak appeared. The reaction was about 10-30 percent complete after 16 hours. An additional 33.6 μl of pyridine was added and the solution heated at 65° C. for 4 hours and at reflux for 16 hours. The solvent was removed under nitrogen and the residue treated with 4 ml of 0.5N NaOH and stirred for 0.5 hour. The solution was extracted with CH2Cl2, acidified with concentrated HCl and filtered. The precipitate was washed with water and dissolved in CH3CN. The resulting solution was heated to reflux, filtered through silica gel and the solvent removed in vacuo to obtain 119 mg (0.321 mmole, 77.2 percent yield) of N-(2,6-dichlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide as a light yellow solid. The product was further purified by washing with acetone, and recrystallizing from refluxing CH3CN to obtain 91.5 mg (0.246 mmole) of product as a white powder, m.p. 263°-265° C. The solution was stirred at room temperature for 16 hours complete after 16 hours at reflux for 16 hours The solvent was removed under nitrogen the residue treated with 4 ml of 0.5N NaOH stirred for 0.5 hour The solution was extracted with CH2Cl2 filtered The precipitate was washed with water dissolved in CH3CN The resulting solution was heated to reflux filtered through silica gel the solvent removed in vacuo

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

実験手順: A solution of 60 ml of benzene, 5.0 g (30.9 mmole) of 2,6-dichloroaniline, 10.6 ml (76.0 mmole) of triethylamine, and 8.08 ml (61.1 mmole) of trimethylsilyl bromide was heated at reflux for 54 hours, cooled, filtered, and the solvent was removed from the filtrate in vacuo. The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide. The residual mixture was filtered into a round-bottomed flask and distilled using a short Vigreaux column to provide 5.43 g (23.2 mmole, 75.0 percent yield) of the N-trimethylsilyl-2,6-dichloroaniline as a 97 percent pure amber oil, bp 74° C.-75° C. at 0.4 mm. at reflux for 54 hours cooled filtered the solvent was removed from the filtrate in vacuo The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide The residual mixture was filtered into a round-bottomed flask distilled

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

実験手順: A solution containing 3.08 g (13.1 mmol) of N-trimethylsilyl-2,6-dichloroaniline and 1.50 g (5.26 mmol) of 5-fluoromethyl-7-chloro-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl chloride in 15 ml of dry acetonitrile was prepared and 0.075 ml (1.05 mmol) of dimethyl sulfoxide was added with stirring at ambient temperature. The mixture was allowed to react over 4 days and the resulting brown solution was then diluted with 150 ml of methylene chloride, washed with water, and dried over magnesium sulfate. The solvent was removed by evaporation under reduced pressure and replaced with hexane to obtain, after collection of the solids and drying, 1.80 g (84 percent of theory) of the 7-chloro analog of the title compound in about 80 percent purity. This was dissolved in 25 ml of dry methanol, the solution cooled to 0°-5° C. and a mixture of 1.70 g (7.89 mmol) of 25 weight percent sodium methoxide in methanol and 5 ml of methanol was added dropwise with stirring over a 10 min. period. The mixture was allowed to react for 10 min. and then about 1 ml of acetic acid was added. The solid that formed was collected, washed with methanol and with water, and dried to obtain 1.15 g (54 percent of theory) of the title compound as a light brown solid. This was extracted by stirring in boiling methanol, cooling, collecting the solids, and drying to obtain 1.09 g of product melting at 189°-191° C. The proton and fluorine nmr spectra were compatible with the assigned structure. was prepared to react over 4 days washed with water dried over magnesium sulfate The solvent was removed by evaporation under reduced pressure to obtain after collection of the solids drying This was dissolved in 25 ml of dry methanol the solution cooled to 0°-5° C. a mixture of 1.70 g (7.89 mmol) of 25 weight percent sodium methoxide in methanol and 5 ml of methanol was added dropwise with stirring over a 10 min. period to react for 10 min. The solid that formed was collected washed with methanol and with water dried

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution consisting of 102.4 mg (0.415 mmole) of 2-chlorosulfonyl-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine, 2.0 ml of acetonitrile, and 33.6 μl (0.415 mmole) of pyridine was stirred 5 minutes. N-trimethylsilyl-2,6-dichloroaniline, 86.9 μl (0.456 mmole) was added. The solution was stirred at room temperature for 16 hours and the reaction monitored by thin layer chromatography and by reverse phase HPLC. The 2-chlorosulfonyl compound gradually disappeared and a new peak appeared. The reaction was about 10-30 percent complete after 16 hours. An additional 33.6 μl of pyridine was added and the solution heated at 65° C. for 4 hours and at reflux for 16 hours. The solvent was removed under nitrogen and the residue treated with 4 ml of 0.5N NaOH and stirred for 0.5 hour. The solution was extracted with CH2Cl2, acidified with concentrated HCl and filtered. The precipitate was washed with water and dissolved in CH3CN. The resulting solution was heated to reflux, filtered through silica gel and the solvent removed in vacuo to obtain 119 mg (0.321 mmole, 77.2 percent yield) of N-(2,6-dichlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide as a light yellow solid. The product was further purified by washing with acetone, and recrystallizing from refluxing CH3CN to obtain 91.5 mg (0.246 mmole) of product as a white powder, m.p. 263°-265° C. The solution was stirred at room temperature for 16 hours complete after 16 hours at reflux for 16 hours The solvent was removed under nitrogen the residue treated with 4 ml of 0.5N NaOH stirred for 0.5 hour The solution was extracted with CH2Cl2 filtered The precipitate was washed with water dissolved in CH3CN The resulting solution was heated to reflux filtered through silica gel the solvent removed in vacuo

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

実験手順: A solution of 60 ml of benzene, 5.0 g (30.9 mmole) of 2,6-dichloroaniline, 10.6 ml (76.0 mmole) of triethylamine, and 8.08 ml (61.1 mmole) of trimethylsilyl bromide was heated at reflux for 54 hours, cooled, filtered, and the solvent was removed from the filtrate in vacuo. The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide. The residual mixture was filtered into a round-bottomed flask and distilled using a short Vigreaux column to provide 5.43 g (23.2 mmole, 75.0 percent yield) of the N-trimethylsilyl-2,6-dichloroaniline as a 97 percent pure amber oil, bp 74° C.-75° C. at 0.4 mm. at reflux for 54 hours cooled filtered the solvent was removed from the filtrate in vacuo The residue was evacuated at 1 mm to remove any excess trimethylsilyl bromide The residual mixture was filtered into a round-bottomed flask distilled