1,2-二溴-1,1,2,2-四氯乙烷

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:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A cooled (−70° C.) solution of 5-bromonicotinic acid (12.6 g, 62.5 mmol) in THF under nitrogen was treated with 2 M lithium diisopropylamide (72 mL, 144 mmol) dropwise over 1 h. The solution stirred for 2.5 h at −55° C. The mixture was then cooled to −70° C. and treated with 1,2-dibromotetrachloroethane (25 g, 77.2 mmol) in portions over 30 min. After 1 h, the reaction mixture was allowed to warm to −20° C. over 2 h and then water (75 mL) was added slowly. The organic layer was then evaporated in vacuo and the aqueous residue was diluted with water (250 mL), then washed with ethyl acetate. The aqueous layer was then acidified to pH 3 by addition of concentrated hydrochloric acid. The precipitated solid was collected by filtration and dried at 60° C. in vacuo to afford 10 g (57%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.75 (s, 1H), 3.2 (br. s, 1H). The mixture was then cooled to −70° C. After 1 h to warm to −20° C. over 2 h The organic layer was then evaporated in vacuo the aqueous residue was diluted with water (250 mL) washed with ethyl acetate The aqueous layer was then acidified to pH 3 by addition of concentrated hydrochloric acid The precipitated solid was collected by filtration dried at 60° C. in vacuo

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

实验步骤: A solution of 2-methoxypyrazolo[1,5-a]pyridine (Reference; Bull. Chem. Soc. Japan, vol. 49(7), 1980–1984(1976)) (7.15 g) in tetrahydrofuran (140 mL) was cooled to −78° C. under a nitrogen stream, and after adding n-butyllithium (1.6M hexane solution: 46 mL) dropwise thereto, the reaction mixture was stirred for 30 minutes. A solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (18.9 g) in tetrahydrofuran (30 mL) was added dropwise to the reaction mixture at −78° C., and stirring was continued for 1 hour. The reaction mixture was raised to room temperature, water was added, and then extraction was performed with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography and the title compound (7.1 g) was obtained as a yellow oil from the n-hexane:ethyl acetate (50:1) fraction. stirring was continued for 1 hour extraction The organic extract was washed with brine dried over anhydrous magnesium sulfate filtered the solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography

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

实验步骤: To a solution of 2-methylpyrazolo[1,5-a]pyridine (Reference; Chem. Pharm. Bull., 1983, 31, 4568–5572) (1.0 g) dissolved in tetrahydrofuran (20 mL) was added n-butyllithium (2.66 M hexane solution; 3.7 mL) dropwise at −78° C. under a nitrogen stream, and the reaction mixture was stirred for 30 minutes. To the reaction mixture was added a solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (2.7 g) in tetrahydrofuran (5 mL) dropwise, and stirring was continued for 30 minutes. After adding saturated aqueous ammonium chloride to the obtained reaction mixture, the temperature was raised to room temperature, water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic extract was separated, then washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography and the title compound (1.34 g) was obtained as a yellow oil from the n-hexane:ethyl acetate (10:1) fraction. stirring was continued for 30 minutes to the obtained reaction mixture The organic extract was separated washed with brine dried over anhydrous magnesium sulfate filtered The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography

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

实验步骤: To a solution of 2-ethylpyrazolo[1,5-a]pyridine (80 mg) dissolved in tetrahydrofuran (1 mL) was added n-butyllithium (1.6M hexane solution: 0.58 mL) dropwise at −78° C. under a nitrogen stream, and the reaction mixture was further stirred for 30 minutes at the same temperature. A solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (196 mg) in tetrahydrofuran (0.5 mL) was added dropwise to the reaction mixture, and stirring was continued for 30 minutes. After raising the temperature to room temperature and adding water to the reaction mixture, extraction was performed with ethyl acetate and the organic extract was washed with water and brine. The obtained organic extract was dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography and the title compound (90 mg) was obtained as a light brown oil from the n-hexane:ethyl acetate (20:1) fraction. stirring was continued for 30 minutes to the reaction mixture, extraction the organic extract was washed with water and brine The obtained organic extract was dried over anhydrous magnesium sulfate filtered the solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography

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

实验步骤: A solution of 3-methoxyphenyl isocyanate and 3-chloro-6-hydrazinopyridazine in acetonitrile was stirred at room temperature for 30 minutes, and 1,2-dibromo-1,1,2,2-tetrachloroethane was added and the mixture was stirred at room temperature for further 2 hours. This reaction solution was combined with triethylamine and triphenylphosphine with cooling in ice, and stirred at room temperature for 3 days. Then, the reaction solution was concentrated under reduced pressure, purified by a standard method to obtain 6-chloro-N-(3-methoxyphenyl)-1,2,4-triazolo[4,3-b]pyridazin-3-amine. Dat (F:276). with cooling in ice stirred at room temperature for 3 days Then, the reaction solution was concentrated under reduced pressure purified by a standard method