伐地那非杂质18

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The compound of formula VI (3.18 g, 0.02 mol) was dissolved into dried tetrahydrofuran (20 mL), and DMAP (0.08 g, 0.6 mmol) and pyridine (5 mL) were added therein. The mixture was heated for 30 minutes at 50° C., cooled, and slowly dropped therein with ethyl oxalyl monochloride (5.46 g, 0.04 mol) under ice bath. After the dropping, the mixture was heated for 4 hours at 70° C., filtered to remove the solid, and evaporated under reduced pressure to remove the solvent. Water (40 mL) was added therein, and the solution was extracted with ethyl acetate (75 mL×3). The liquid was separated, the combined organic phase was washed with water (30 mL) and saturated saline (30 mL×2) respectively, dried over anhydrous sodium sulfate, and rotarily evaporated to remove the solvent therein. NaHCO3 (1.26 g, 0.015 mol) and methanol (20 mL) were added therein, and the mixture was refluxed for 2 hours, filtered, and evaporated under reduced pressure to remove solvent to obtain a yellow oil, i.e., ethyl 3-butyramido-2-oxo-butyrate, which was directly used in the next step without separation. were added cooled slowly dropped After the dropping, the mixture was heated for 4 hours at 70° C. filtered to remove the solid evaporated under reduced pressure to remove the solvent Water (40 mL) was added the solution was extracted with ethyl acetate (75 mL×3) The liquid was separated the combined organic phase was washed with water (30 mL) and saturated saline (30 mL×2) respectively dried over anhydrous sodium sulfate rotarily evaporated to remove the solvent the mixture was refluxed for 2 hours filtered evaporated under reduced pressure to remove solvent

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The compound of formula VI (9.54 g, 0.06 mol) was dissolved into dried tetrahydrofuran (60 mL), and DMAP (0.24 g, 2.0 mmol) and pyridine (15 mL) were added therein. The mixture was heated for 30 minutes at 50° C., cooled, and slowly dropped with ethyl oxalyl monochloride (16.4 g, 0.12 mol) under an ice bath. After the dropping, the mixture was heated for 4 hours at 70° C., filtered to remove the solid, and evaporated to remove the solvent under reduced pressure. Water (100 mL) was added therein, and the product was extracted with ethyl acetate (120 mL×3). The liquid was separated, and the combined organic phase was washed by water (90 mL) and saturated saline (50 mL×2) respectively, dried over anhydrous sodium sulfate, and rotarily evaporated to remove the solvent. NaHCO3 (3.8 g, 0.045 mol) and methanol (50 mL) were added therein, and the reaction mixture was refluxed for 2 hours, filtered, and evaporated off the solvent under reduced pressure to obtain a yellow oil, i.e., ethyl 3-butyramido-2-oxo-butyrate, which was directly used in the next step without separation. were added cooled After the dropping, the mixture was heated for 4 hours at 70° C. filtered to remove the solid evaporated to remove the solvent under reduced pressure Water (100 mL) was added the product was extracted with ethyl acetate (120 mL×3) The liquid was separated the combined organic phase was washed by water (90 mL) and saturated saline (50 mL×2) respectively dried over anhydrous sodium sulfate rotarily evaporated to remove the solvent the reaction mixture was refluxed for 2 hours filtered evaporated off the solvent under reduced pressure

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The compound of formula VI (3.18 g, 0.02 mol) was dissolved into dried tetrahydrofuran (20 mL), followed by addition of DMAP (0.08 g, 0.6 mmol) and pyridine (5 mL) therein. The mixture was heated for 30 minutes at 50° C., and then cooled. Under ice bath, ethyl oxalyl monochloride (5.46 g, 0.04 mol) was slowly dropped therein. After the dropping, the mixture was heated for 4 hours at 70° C. The solid was filtered off and the solvent was evaporated off under reduced pressure. Water (40 mL) was added therein, and the product was extracted by using ethyl acetate (75 mL×3). The liquid was separated, and the combined organic phase was washed by water (30 mL) and saturated saline (30 mL×2) respectively, and dried over anhydrous sodium sulfate. After the solvent therein was removed by rotary evaporation, NaHCO3 (1.26 g, 0.015 mol) and methanol (20 mL) were added therein, and the mixture was refluxed for 2 hours. After filtration, the solvent was removed by evaporation under reduced pressure to give a yellow oil, i.e., ethyl 3-butyramido-2-oxo-butyrate, which is directly used in the next step without purification. cooled After the dropping, the mixture was heated for 4 hours at 70° C The solid was filtered off the solvent was evaporated off under reduced pressure Water (40 mL) was added the product was extracted The liquid was separated the combined organic phase was washed by water (30 mL) and saturated saline (30 mL×2) respectively dried over anhydrous sodium sulfate were added the mixture was refluxed for 2 hours After filtration the solvent was removed by evaporation under reduced pressure

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

实验步骤: Aminoguanidine bicarbonate (2.4 g) was suspended in a solution of ethyl 3-butyramido-2-oxo-butyrate (3.8 g) in absolute ethanol (40 ml) and the mixture was heated under reflux for 5 hours. During this period aminoguanidine bicarbonate gradually dissolved and a new product precipitated as a white solid. The mixture was cooled and the solid (2.62 g) collected and taken up in 2 N hydrochloric acid (30 ml). The solution was filtered to remove a small amount of undissolved solid, then adjusted to pH 8 by adding solid sodium carbonate. The triazinone separated as a white solid which was collected, washed with water and dried in vacuo at 100° to give material m.p. 308° (dec.), (2.0 g) (50% approx.). the mixture was heated under reflux for 5 hours a new product precipitated as a white solid The mixture was cooled the solid (2.62 g) collected The solution was filtered to remove a small amount of undissolved solid by adding solid sodium carbonate The triazinone separated as a white solid which was collected washed with water dried in vacuo at 100°

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

实验步骤: To an ice-cold solution of acetamidine hydrochloride (66.2 g) in absolute ethanol (600 ml) was slowly added a solution of hydrazine hydrate (35 g) in absolute ethanol (20 ml) over 20 minutes. After completion of the addition stirring was continued at room temperature for 10 minutes. A solution of ethyl 3-butyramido-2-oxo-butyrate (151 g) in absolute ethanol (100 ml) was then added and the mixture heated at 65°-70° with stirring for 20 hours. The precipitated ammonium chloride was removed by filtration and the filtrate concentrated in vacuo whereupon the triazinone separated. Ethyl acetate (ca. 300 ml) was added to aid the precipitation and the solid was collected. The filtrate was concentrated to give a second crop which was combined with the first and recrystallised from ethanol, 28.6 g. A further recrystallisation from ethanol afforded an analytical sample, m.p. 235°-237°. After completion of the addition the mixture heated at 65°-70° with stirring for 20 hours The precipitated ammonium chloride was removed by filtration the filtrate concentrated in vacuo whereupon the triazinone separated Ethyl acetate (ca. 300 ml) was added the precipitation the solid was collected The filtrate was concentrated to give a second crop which recrystallised from ethanol, 28.6 g A further recrystallisation from ethanol afforded an analytical sample, m.p. 235°-237°