氨基甲酰乙酸乙酯

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

实验步骤: Prepared from 1-benzyl-hexahydro-4-azepinone with ethyl formate and ethyl malonamate in the presence of sodium hydride.

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

实验步骤: To a stirred solution of 2.0 g (0.0102 mol) of 4-butoxy-1,1,1-trifluoro-3-buten-2-one (VIIIa) and 1.3 g (0.0102 mol) of ethyl malonate monoamide in 10 mL methyl alcohol was added 2.2 mL (0.0102 mol) of a 25% solution of sodium methoxide in methanol. The solution turned into a thick yellow suspension which was refluxed overnight. The suspension was cooled to room temperature, poured into water, acidified with one normal hydrochloric acid and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to afford 1.7 g (74%) of a yellow solid. m.p. 63°-64° C.; 1H NMR (CDCl3) δ4.0 (3H, s), 7.33 (1H, d, J=8 Hz), 8.4 (1H, d, J=8 Hz); IR (mineral oil) 3080, 1675 (br), 1605, 1450, 1375 cm-1. was refluxed overnight extracted with methylene chloride The combined organic layers were washed with brine dried over magnesium sulfate evaporated

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

实验步骤: To a stirred solution of 2.0 g (0.0102 mol) of 4-butoxy-1,1,1-trifluoro-3-buten-2-one (VIIIa) and 1.3 g (0.0102 mol) of ethyl malonate monoamide in 10 mL methyl alcohol was added 2.2 mL (0.0102 mol) of a 25% solution of sodium methoxide in methanol. The solution turned into a thick yellow suspension which was refluxed overnight. The suspension was cooled to room temperature, poured into water, acidified with one normal hydrochloric acid and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to afford 1.7 g (74%) of a yellow solid. m.p. 63°-64° C.; 1H NMR (CDCl3) δ4.0 (3H, s), 7.33 (1H, d, J=8 Hz), 8.4 (1H, d, J=8 Hz); IR (mineral oil) 3080, 1675 (br), 1605, 1450, 1375 cm-1. was refluxed overnight extracted with methylene chloride The combined organic layers were washed with brine dried over magnesium sulfate evaporated

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

实验步骤: 4-(Trimethylsilanylmethoxy)benzaldehyde (obtained in step 1 of Example 1) (3 g, 0.015 mol) and ethyl malonate monoamide (2.1 g, 0.016 mol) in 10 ml of dry toluene in the presence of 0.24 ml of piperidine and 0.14 g of acetic acid are refluxed for 3 hours in a reactor equipped with Dean-Stark apparatus. The water formed is removed azeotropically. The mixture is cooled and the toluene is removed by distillation. The reaction mixture is taken up in 50 ml of diisopropyl ether. The organic phase is washed 3 times with water, dried over sodium sulfate and filtered, and the solvent is evaporated off under vacuum. The yellow gum obtained is crystallized from a diisopropyl ether/heptane mixture. 1.8 g (yield: 37%) of the derivative of Example 8 are obtained in the form of a pale yellow solid: equipped with Dean-Stark apparatus is removed azeotropically The mixture is cooled the toluene is removed by distillation The organic phase is washed 3 times with water dried over sodium sulfate filtered the solvent is evaporated off under vacuum The yellow gum obtained is crystallized from a diisopropyl ether/heptane mixture 1.8 g (yield: 37%) of the derivative of Example 8 are obtained in the form of a pale yellow solid

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

实验步骤: 4-(Trimethylsilanylmethoxy)benzaldehyde (obtained in step 1 of Example 1) (3 g, 0.015 mol) and ethyl malonate monoamide (2.1 g, 0.016 mol) in 10 ml of dry toluene in the presence of 0.24 ml of piperidine and 0.14 g of acetic acid are refluxed for 3 hours in a reactor equipped with Dean-Stark apparatus. The water formed is removed azeotropically. The mixture is cooled and the toluene is removed by distillation. The reaction mixture is taken up in 50 ml of diisopropyl ether. The organic phase is washed 3 times with water, dried over sodium sulfate and filtered, and the solvent is evaporated off under vacuum. The yellow gum obtained is crystallized from a diisopropyl ether/heptane mixture. 1.8 g (yield: 37%) of the derivative of Example 8 are obtained in the form of a pale yellow solid: equipped with Dean-Stark apparatus is removed azeotropically The mixture is cooled the toluene is removed by distillation The organic phase is washed 3 times with water dried over sodium sulfate filtered the solvent is evaporated off under vacuum The yellow gum obtained is crystallized from a diisopropyl ether/heptane mixture 1.8 g (yield: 37%) of the derivative of Example 8 are obtained in the form of a pale yellow solid

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 200 g of ethyl β-ethoxy-β-iminopropionate hydrochloride were placed into a 1,000 ml flask and heated at 110° C. on an oil bath for 2 hours. The reaction mixture was redissolved with 500 ml of acetone, filtered by washing on the filter with other solvent. The filtrate was dried under vacuum and the obtained oily residue was grinded in 1,500 ml of ethyl ether. 108 g of a crystalline product were obtained. Upon TLC analysis, the product proved to be pure. filtered by washing on the filter with other solvent The filtrate was dried under vacuum the obtained oily residue was grinded in 1,500 ml of ethyl ether

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

实验步骤: Prepared from 1-benzyl-hexahydro-4-azepinone with ethyl formate and ethyl malonamate in the presence of sodium hydride.

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

实验步骤: To a stirred solution of 2.0 g (0.0102 mol) of 4-butoxy-1,1,1-trifluoro-3-buten-2-one (VIIIa) and 1.3 g (0.0102 mol) of ethyl malonate monoamide in 10 mL methyl alcohol was added 2.2 mL (0.0102 mol) of a 25% solution of sodium methoxide in methanol. The solution turned into a thick yellow suspension which was refluxed overnight. The suspension was cooled to room temperature, poured into water, acidified with one normal hydrochloric acid and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to afford 1.7 g (74%) of a yellow solid. m.p. 63°-64° C.; 1H NMR (CDCl3) δ4.0 (3H, s), 7.33 (1H, d, J=8 Hz), 8.4 (1H, d, J=8 Hz); IR (mineral oil) 3080, 1675 (br), 1605, 1450, 1375 cm-1. was refluxed overnight extracted with methylene chloride The combined organic layers were washed with brine dried over magnesium sulfate evaporated

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

实验步骤: To a stirred solution of 2.0 g (0.0102 mol) of 4-butoxy-1,1,1-trifluoro-3-buten-2-one (VIIIa) and 1.3 g (0.0102 mol) of ethyl malonate monoamide in 10 mL methyl alcohol was added 2.2 mL (0.0102 mol) of a 25% solution of sodium methoxide in methanol. The solution turned into a thick yellow suspension which was refluxed overnight. The suspension was cooled to room temperature, poured into water, acidified with one normal hydrochloric acid and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to afford 1.7 g (74%) of a yellow solid. m.p. 63°-64° C.; 1H NMR (CDCl3) δ4.0 (3H, s), 7.33 (1H, d, J=8 Hz), 8.4 (1H, d, J=8 Hz); IR (mineral oil) 3080, 1675 (br), 1605, 1450, 1375 cm-1. was refluxed overnight extracted with methylene chloride The combined organic layers were washed with brine dried over magnesium sulfate evaporated

反应条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl malonamate (34.7 g, 0.26 mole) and methanol (100 ml) were placed in a flash equipped with a dropping funnel, a stirrer, and a soda lime trap (to exclude CO2). The flask was cooled to about 15° C. in an ice-water bath. Freshly prepared biguanide (26.3 g, 0.26 mole, in 250 ml methanol) was added, with stirring, over 35 min at 15°-20° C. A white precipitate began to form within 8-9 min. The mixture was allowed to stir overnight at room temperature. It was then cooled to 15° C., and the white precipitate was filtered, washed with cold water to remove sodium sulfate, and finally washed with cold methanol. A crude yield of 32.7 g (76%) was obtained. A pure sample recrystallized from water had a mp of 295°-96° C. (dec.) when placed in a preheated bath at 295° C. Anal. calcd. for C5H8N6O: C, 36.59; H, 4.91; N, 48.76. Found: C, 36.73; H, 5.08; N, 48.51. to form within 8-9 min to stir overnight at room temperature It was then cooled to 15° C. the white precipitate was filtered washed with cold water to remove sodium sulfate finally washed with cold methanol A crude yield of 32.7 g (76%) was obtained A pure sample recrystallized from water placed in a preheated bath at 295° C

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

实验步骤: Biguanide was prepared fresh by refluxing anhydrous biguanide sulfate in a methanol solution of freshly prepared sodium methylate by the method of Slotta et al. (Slotta, K. H., Tschesche, R., Ber. Dtsch. Chem. Ges. 1929, B62, 1390-1398). The biguanide was used in solution as prepared for all of the reactions. Because sodium sulfate formed in the preparation of biguanide did not interfere with subsequent reactions, it was not necessary to separate it from the biguanide. Ethyl malonamate used in the preparation of Ib (see Example I below) was prepared as follows by methods of Galat and Marguery (Galat, A., J. Am. Chem. Soc. 1948, 70, 2596 and Marguery, M. F., Bull. Soc. Chem. France 1905, 33, 541; J. Recherces Centr. Nalt. Recherche Sci., Labs. Bellevue (Pairs) 1959, 47, 147), through Chem. Abstr. 1962, 56, 4744g.): Diethyl malonate was converted to the mono-potassium salt of the half-ester. The latter was converted to ethyl malonyl chloride, which in turn was reacted with anhydrous ammonia in ice-cold ether to form ethyl malonamate. to separate it from the biguanide Ethyl malonamate used in the preparation of Ib (see Example I below) was prepared

反应条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl malonamate (34.7 g, 0.26 mole) and methanol (100 ml) were placed in a flash equipped with a dropping funnel, a stirrer, and a soda lime trap (to exclude CO2). The flask was cooled to about 15° C. in an ice-water bath. Freshly prepared biguanide (26.3 g, 0.26 mole, in 250 ml methanol) was added, with stirring, over 35 min at 15°-20° C. A white precipitate began to form within 8-9 min. The mixture was allowed to stir overnight at room temperature. It was then cooled to 15° C., and the white precipitate was filtered, washed with cold water to remove sodium sulfate, and finally washed with cold methanol. A crude yield of 32.7 g (76%) was obtained. A pure sample recrystallized from water had a mp of 295°-96° C. (dec.) when placed in a preheated bath at 295° C. Anal. calcd. for C5H8N6O: C, 36.59; H, 4.91; N, 48.76. Found: C, 36.73; H, 5.08; N, 48.51. to form within 8-9 min to stir overnight at room temperature It was then cooled to 15° C. the white precipitate was filtered washed with cold water to remove sodium sulfate finally washed with cold methanol A crude yield of 32.7 g (76%) was obtained A pure sample recrystallized from water placed in a preheated bath at 295° C