反应详情

温度

0 °C

The title compound was prepared from 3-(5,6-dimethyl-[1,2,4]triazin-3-yl)-benzoic acid methyl ester [prepared by the following procedure: A solution of 3-chlorocarbonyl-benzoic acid methyl ester (31.6 g, 0.15 mol) in Et2O (0.15 l) was added over 15 min at 0-5° C. to a solution of hydrazinecarboxylic acid tert-butyl ester (19.9 g, 0.1 mol) and pyridine (13.3 ml, 0.165 mol) in Et2O (0.6 l). The mixture was stirred for 1 h at 0° C. and for 1 h at RT, diluted with AcOEt and washed successively with 1N HCl, sat. NaHCO3-sol. and brine. The organic layer was dried and evaporated to give 3-(N′-tert-butoxycarbonyl-hydrazinocarbonyl)-benzoic acid (31.5 g) as white solid. A sample of this material (29.4 g, 0.1 mol) was stirred in a mixture of MeOH (0.1 l) and 1 N KOH (0.2 l) for 18 h at RT The solution was concentrated in vacuum and then washed with AcOEt. The aqueous phase was acidified to pH 1 with 3N HCl and the precipitate formed was isolated by filtration, dried and then stirred with TFA (0.3 l) at RT for 40 min. The mixture was evaporated in vacuum and the residue was triturated with Et2O/EtOH (10:1) to give 3-hydrazinocarbonyl-benzoic acid as a white solid (16.2 g). A solution of this material (3.6 g, 20 mmol) and 1,3-butandione (1.89 g, 22 mmol) in MeOH (20 ml) was stirred at RT for 1 h. The mixture was evaporated in vacuum and the residue was heated in an autoclave in 5N NH3-MeOH (30 mL) at 150° C. for 3 h. The mixture was cooled and partitionned between AcOEt and sat. NaHCO3-solution. The aqueous phase was acidified to pH 3 with 3N HCl and extracted with AcOEt. The crude product obtained from the AcOEt extract was esterified by heating in 1N HCl-MeOH (80 mL) for 18 h at 50° C. The crude product was purified by chromatography (silica gel, AcOEt) to give the methyl ester as light yellow solid (1.21 g).] (1.21 g, 5 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light brown solid (1.78 g, crude product).

1. customprepared by the following procedure
2. washwashed successively with 1N HCl, sat. NaHCO3-sol
3. customThe organic layer was dried
4. customevaporated