* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium hydroxide; In tetrahydrofuran; dichloromethane; di-isopropyl ether; water;
7-Bromo-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one To a suspension of 51.2 g of 60percent sodium hydride in oil (1.28 mole) in 1 liter of tetrahydrofuran heated to reflux, and under nitrogen atmosphere was added a solution of 144 g (0.61 mole) of 5-bromo-2-chloropyridine-3-carboxylic acid and 61.6 g (0.61 mole) of N-methyl-3-pyrrolidinol in 1 liter of tetrahydrofuran dropwise at reflux (~1 hr). Heating was continued at reflux with vigorous agitation for 1.5 hr. After cooling, approximately 5 ml of water was added and the mixture soon solidified. Additional tetrahydrofuran was added to aid in stirring. The mixture was filtered, washed with several portions of tetrahydrofuran, and dried at 50° C., 0.05 mm Hg, overnight to give 190 g of crude sodium salt. The entire amount of crude sodium salt (190 g) was added slowly to 1000 g of thionyl chloride cooled in an ice bath. The reaction mixture was stirred for 10 minutes at ~10° C. and 10 minutes at room temperature. Excess thionyl chloride was removed by rotary evaporation at 65° C., 30 mm Hg and the residue azetroped twice with toluene. The residue was taken up in ~1 liter of methylene chloride and diisopropylethyl amine and was added slowly until the solution just turned basic. The mixture was stirred for 1 hr at room temperature and washed successively with 2*200 ml of 1N hydrochloride acid, 2*200 ml of dilute sodium hydroxide and 100 ml of water. The organic phase was dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The black residue was triturated 5 times with 5percent toluene in diisopropyl ether to give 60 g (31percent) of light brown crystals. A sample was recrystallized from diisopropyl ether, m.p. 71°-75° C. Analysis: Calculated for C11 H12 N2 O2 BrCl: C, 41.34; H, 3.79; N, 8.77. Found: C, 41.35; H, 3.81; N, 8.89.
60 g (31%)
With sodium hydroxide; In tetrahydrofuran; dichloromethane; di-isopropyl ether; water;
7-Bromo-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one To a suspension of 51.2 g of 60percent sodium hydride in oil (1.28 mole) in 1 liter of tetrahydrofuran heated to reflux, and under nitrogen atmosphere was added a solution of 144 g (0.61 mole) of 5-bromo-2-chloropyridine-3-carboxylic acid and 61.6 g (0.61 mole) of N-methyl-3-pyrrolidinol in 1 liter of tetrahydrofuran dropwise at reflux (~1 hr). Heating was continued at reflux with vigorous agitation for 1.5 hr. After cooling, approximately 5 ml of water was added and the mixture soon solidified. Additional tetrahydrofuran was added to aid in stirring. The mixture was filtered, washed with several portions of tetrahydrofuran, and dried at 50° C., 0.05 mm Hg, overnight to give 190 g of crude sodium salt. The entire amount of crude sodium salt (190 g) was added slowly to 1000 g of thionyl chloride cooled in an ice bath. The reaction mixture was stirred for 10 minutes at ~10° C. and 10 minutes at room temperature. Excess thionyl chloride was removed by rotary evaporation at 65° C., 30 mm Hg and the residue azetroped twice with toluene. The residue was taken up in ~1 liter of methylene chloride and dissopropylethyl amine and was added slowly until the solution just turned basic. The mixture was stirred for 1 hr at room temperature and washed successively with 2*200 ml of 1N hydrochloride acid, 2*200 ml of dilute sodium hydroxide and 100 ml of water. The organic phase was dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The black residue was triturated 5 times with 5percent toluene in diisopropyl ether to give 60 g (31percent) of light brown crystals. A sample was recrystallized from diisopropyl ether, m.p. 71°-75° C. Analysis: Calculated for C11 H12 N2 O2 BrCl: C, 41.34; H, 3.79; N, 8.77. Found: C, 41.35; H, 3.81; N, 8.89.
5-bromo-2-(2-methyl-3-trifluoromethylanilino)-nicotinic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydrogencarbonate; In methanol; sodium hydroxide;
EXAMPLE 2 5-Bromo-2-(2-methyl-3-trifluoromethylanilino) nicotinic acid Heat in an oil bath at 170° C. a mixture of 15 g. of 5-bromo-2-chloro-nicotinic acid, 12.2 g. of <strong>[54396-44-0]2-methyl-3-trifluoromethyl aniline</strong> and 60 g. of phenol for three hours. Treat the resulting reaction mixture with ether and 5percent sodium bicarbonate solution, concentrate and steam distil to obtain an oily residue. Dissolve the oily residue in dilute sodium hydroxide solution, acidify with dilute hydrochloric acid and filter. Recrystallize the product from methanol to yield 5-bromo-2-(2-methyl-3-trifluoromethylanilino) nicotinic acid, m.p. 222°-224° C.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
