diethyl 2-(aminomethylidene)propanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 25 g. of diethyl aminomethylenemalonate, 18 g. of phenylacetone dimethylketal, 300 ml. of dry diphenyl ether and 1.0 g. of TSA.H2O were mixed and heated under a nitrogen atmosphere at 135°-145° C. for three hours. The mixture was then brought to reflux. After 30 minutes the solution was cooled and extracted with 200 ml. of 21/2 aqueous NaOH solution. The basic extracts were acidified yielding a precipitate of ethyl 6-methyl-5-phenyl-4-oxonicotinate. Recrystallization of this material from methylene chloride/ether provided 12.3 g. of white solid, m.p.=178°-180° C. heated under a nitrogen atmosphere at 135°-145° C. for three hours to reflux After 30 minutes the solution was cooled extracted with 200 ml

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

実験手順: 25 g. of diethyl aminomethylenemalonate, 18 g. of phenylacetone dimethylketal, 300 ml. of dry diphenyl ether and 1.0 g. of TSA.H2O were mixed and heated under a nitrogen atmosphere at 135°-145° C. for three hours. The mixture was then brought to reflux. After 30 minutes the solution was cooled and extracted with 200 ml. of 21/2 aqueous NaOH solution. The basic extracts were acidified yielding a precipitate of ethyl 6-methyl-5-phenyl-4-oxonicotinate. Recrystallization of this material from methylene chloride/ether provided 12.3 g. of white solid, m.p.=178°-180° C. heated under a nitrogen atmosphere at 135°-145° C. for three hours to reflux After 30 minutes the solution was cooled extracted with 200 ml

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

実験手順: 25 g. of diethyl aminomethylenemalonate, 18 g. of phenylacetone dimethylketal, 300 ml. of dry diphenyl ether and 1.0 g. of TSA.H2O were mixed and heated under a nitrogen atmosphere at 135°-145° C. for three hours. The mixture was then brought to reflux. After 30 minutes the solution was cooled and extracted with 200 ml. of 21/2% aqueous NaOH solution. The basic extracts were acidified yielding a precipitate of ethyl 6-methyl-5-phenyl-4-oxonicotinate. Recrystallization of this material from methylene chloride/ether provided 12.3 g. of white solid, m.p.=178°-180° C. heated under a nitrogen atmosphere at 135°-145° C. for three hours to reflux After 30 minutes the solution was cooled extracted with 200 ml

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

実験手順: 25 g. of diethyl aminomethylenemalonate, 18 g. of phenylacetone dimethylketal, 300 ml. of dry diphenyl ether and 1.0 g. of TSA.H2O were mixed and heated under a nitrogen atmosphere at 135°-145° C. for three hours. The mixture was then brought to reflux. After 30 minutes the solution was cooled and extracted with 200 ml. of 21/2% aqueous NaOH solution. The basic extracts were acidified yielding a precipitate of ethyl 6-methyl-5-phenyl-4-oxonicotinate. Recrystallization of this material from methylene chloride/ether provided 12.3 g. of white solid, m.p.=178°-180° C. heated under a nitrogen atmosphere at 135°-145° C. for three hours to reflux After 30 minutes the solution was cooled extracted with 200 ml

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

実験手順: A mixture of 12.6 g of 4-ethylcyclohexanone, 17.0 g of diethyl aminomethylenemalonate, and 950 mg of p-toluenesulfonic acid in 170 ml of toluene is heated at reflux for 48 hours with a water separator, under nitrogen atmosphere. The solvent is removed under nitrogen atmosphere and under vacuum, and the residue purified by flash column chromatooraphy on a silica qel column eluted with methylene chloride. The desired product, diethyl N-(4-ethylcyclohexen-1-yl)-aminomethylenemalonate is obtained as an oil. The purified product in 90 ml Dowtherm is aded to 300 ml Dowtherm preheated to 250° under nitrogen atmosphere. After heating at 240°-245° for 4 hours the reaction mixture is cooled and allowed to stand at room temperature overnight. The precipitate which formed is filtered off, washed with hexane and air-dried. Recrystallization form isopropanol after treatment with decolorizing carbon affords ethyl 4-hydroxy-6-ethyl-5,6,7,8-tetrahydroquinoline-3-carboxylate m.p. 218°-220°. is heated The solvent is removed under nitrogen atmosphere and under vacuum the residue purified by flash column chromatooraphy on a silica qel column eluted with methylene chloride

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-aminomethylene-malonic acid diethyl ester (0.75 g, 4.0 mmol) and phenyl isocyanate (0.57 g, 4.4 mmol) in 1,2-dichloroethane (20 mL) was added N,N-diisopropylethylamine (0.77 mL, 4.4 mmol) and heated at 100° C. 6 h. The mixture was cooled and filtered. The solids were purified by column chromatography with 0-5% MeOH in methylene chloride. This intermediate urea was suspended in ethanol (10 mL) and 21% NaOEt in ethanol (1.29 mL, 4.0 mmol) was added. After 18 h the solvent was removed under vacuum and the residue was slurred in ethyl acetate. The organics were washed with 1M citric acid solution, water and brine. The solvent was removed under vacuum and the residue was purified by chromatography with 0-5% MeOH in dichloromethane to give 0.50 g (40%). The ester was alkylated and hydrolyzed using methods for example 92 to give 1-ethyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid. 1H NMR (DMSO) δ: 12.65 (bs, 1H), 8.82 (s, 1H), 7.54-7.43 (m, 3H), 7.32-7.29 (m, 2H), 4.02 (q, 2H, J=7.1 Hz), 1.26 (t, 3H, J=7.1 Hz). 6 h The mixture was cooled filtered The solids were purified by column chromatography with 0-5% MeOH in methylene chloride After 18 h the solvent was removed under vacuum The organics were washed with 1M citric acid solution, water and brine The solvent was removed under vacuum the residue was purified by chromatography with 0-5% MeOH in dichloromethane to give 0.50 g (40%)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 25.0 g of cyclodecanone, 60.7 g of diethyl aminomethylenemalonate, 1.54 g of p-toluenesulfonic acid monohydrate in 500 ml xylene is refluxed 2 weeks under argon, collecting the distillate in a Dean-Stark trap. The solution is then decanted and solvent is removed. The residual oil is triturated twice with hexane and the combined hexane extract is concentrated to yield an oil which is flash chromatographed on 600 g of silica gel using 99:1 methylene chloride ethyl acetate as eluent. A forerun containing cyclodecanone is discarded and the fractions containing the product are combined and concentrated to dryness to give diethyl N-(1-cyclodecenyl)-aminomethylenemalonate as an oil. is refluxed 2 weeks under argon collecting the distillate in a Dean-Stark trap The solution is then decanted solvent is removed The residual oil is triturated twice with hexane the combined hexane extract is concentrated to yield an oil which chromatographed on 600 g of silica gel using 99:1 methylene chloride ethyl acetate as eluent A forerun containing cyclodecanone the fractions containing the product concentrated to dryness