反应详情

温度

20 °C

17 ml dry dimethylformamide in 40 ml dry dioxan are cooled to 0° C. and 1.0 g (7.9 mMole) oxalyl chloride added dropwise thereto under an atmosphere of nitrogen. After 20 minutes, 2.7 g (6.9 mMole) (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid (European Patent Application 173 933) are added portionwise thereto at 0° C. and the reaction mixture is warmed to 20° C. After 30 minutes at 20° C., this solution is added dropwise to a solution, cooled to 0° C., of 2.6 g (15.8 mMole) N-benzyl-N-methylethylene-diamine in 20 ml n-hexane. After warming to 20° C., the reaction mixture is stirred for 30 minutes then, with renewed ice cooling, 2 N aqueous sodium carbonate solution is added dropwise thereto and the reaction mixture is extracted twice with dichloromethane. The dichloromethane solutions are washed with water and dried over anhydrous sodium sulphate. The solvent is removed in a vacuum and the residue is chromatographed on silica gel with dichloromethane/methanol (9:1 v/v). The fraction with the Rf of 0.5 is isolated, dissolved in diethyl ether and the dihydrochloride precipitated out with hydrogen chloride in diethyl ether. This is recrystallized twice from acetonitrile. There is obtained (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid 2-(N-benzyl-N-methylamino)-ethylamide dihydrochloride in the form of colorless crystals; mp 178°-180° C.

1. waitAfter 30 minutes at 20° C.
2. additionthis solution is added dropwise to a solution
3. temperatureAfter warming to 20° C.
4. extractionthe reaction mixture is extracted twice with dichloromethane
5. washThe dichloromethane solutions are washed with water
6. dry with materialdried over anhydrous sodium sulphate
7. customThe solvent is removed in a vacuum
8. customthe residue is chromatographed on silica gel with dichloromethane/methanol (9:1 v/v)
9. customThe fraction with the Rf of 0.5 is isolated
10. customthe dihydrochloride precipitated out with hydrogen chloride in diethyl ether
11. customThis is recrystallized twice from acetonitrile