2-[Methoxy(phenyl)methylidene]propanedinitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After dissolving (methoxyphenylmethylene)methane-1,1-dicarbonitrile (15.10 g) and β-alanine ethyl ester hydrochloride (15.11 g) in acetonitrile (300 mL), triethylamine (23.00 mL) was added and the mixture was stirred for 10 minutes at room temperature. After confirming complete consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1), the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the residue, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue. Methyl bromoacetate (16.00 mL) was added thereto and the mixture was heated to reflux for 40 minutes. After cooling the mixture to room temperature, it was allowed to stand, the supernatant was separated by decantation, and the solvent was distilled off under reduced pressure. The residue was combined with the solid portion remaining after decantation, ethyl acetate and water were added, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was passed through a chromatography column packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities, to obtain the title compound as a crude product (35.31 g). was added consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1) the solvent was distilled off under reduced pressure Ethyl acetate and water were added to the residue, and extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue Methyl bromoacetate (16.00 mL) was added the mixture was heated to reflux for 40 minutes After cooling the mixture to room temperature the supernatant was separated by decantation the solvent was distilled off under reduced pressure were added extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After dissolving (methoxyphenylmethylene)methane-1,1-dicarbonitrile (15.10 g) and β-alanine ethyl ester hydrochloride (15.11 g) in acetonitrile (300 mL), triethylamine (23.00 mL) was added and the mixture was stirred for 10 minutes at room temperature. After confirming complete consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1), the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the residue, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue. Methyl bromoacetate (16.00 mL) was added thereto and the mixture was heated to reflux for 40 minutes. After cooling the mixture to room temperature, it was allowed to stand, the supernatant was separated by decantation, and the solvent was distilled off under reduced pressure. The residue was combined with the solid portion remaining after decantation, ethyl acetate and water were added, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was passed through a chromatography column packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities, to obtain the title compound as a crude product (35.31 g). was added consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1) the solvent was distilled off under reduced pressure Ethyl acetate and water were added to the residue, and extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue Methyl bromoacetate (16.00 mL) was added the mixture was heated to reflux for 40 minutes After cooling the mixture to room temperature the supernatant was separated by decantation the solvent was distilled off under reduced pressure were added extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl N-(2-aminoethyl)carbamate (10.6 g) was added to a solution of (methoxyphenylmethylene)methane-1,1-dicarbonitrile (10.4 g) in acetonitrile (350 mL), and the mixture was stirred for 10 minutes. Anhydrous cesium carbonate (65.1 g) and methyl bromoacetate (13.5 mL) were added, and the mixture was heated to reflux for 1 hour. After cooling the mixture to room temperature, it was allowed to stand, the supernatant was separated by decantation, and the solvent was distilled off under reduced pressure. The concentrated residue was combined with the solid portion remaining after decantation, ethyl acetate and water were added, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 2/1) to obtain the title compound (20.6 g, yield: 95%) as a yellow transparent oil. The NMR and ESI/MS data for this compound-are shown below. the mixture was heated to reflux for 1 hour the supernatant was separated by decantation the solvent was distilled off under reduced pressure were added extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate 2/1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2.50 g of ethyl 2-pyridylacetate and 2.79 g of 2-cyano-3-methoxy-3-phenylacrylonitrile was dissolved in 15 ml of dry N,N-dimethylformamide. To the solution was added 0.61 g of 60% sodium hydride and the reaction mixture was stirred for 1 hour at 60° C. The reaction mixture was poured into ice-water, and precipitated crystals were collected by filtration, washed with water and dried under vacuum to obtain 2.50 g of 3-cyano-1-ethoxycarbonyl-4-imino-2-phenyl-4H-quinolizine. precipitated crystals were collected by filtration washed with water dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After dissolving (methoxyphenylmethylene)methane-1,1-dicarbonitrile (15.10 g) and β-alanine ethyl ester hydrochloride (15.11 g) in acetonitrile (300 mL), triethylamine (23.00 mL) was added and the mixture was stirred for 10 minutes at room temperature. After confirming complete consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1), the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the residue, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue. Methyl bromoacetate (16.00 mL) was added thereto and the mixture was heated to reflux for 40 minutes. After cooling the mixture to room temperature, it was allowed to stand, the supernatant was separated by decantation, and the solvent was distilled off under reduced pressure. The residue was combined with the solid portion remaining after decantation, ethyl acetate and water were added, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was passed through a chromatography column packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities, to obtain the title compound as a crude product (35.31 g). was added consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1) the solvent was distilled off under reduced pressure Ethyl acetate and water were added to the residue, and extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue Methyl bromoacetate (16.00 mL) was added the mixture was heated to reflux for 40 minutes After cooling the mixture to room temperature the supernatant was separated by decantation the solvent was distilled off under reduced pressure were added extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl N-(2-aminoethyl)carbamate (10.6 g) was added to a solution of (methoxyphenylmethylene)methane-1,1-dicarbonitrile (10.4 g) in acetonitrile (350 mL), and the mixture was stirred for 10 minutes. Anhydrous cesium carbonate (65.1 g) and methyl bromoacetate (13.5 mL) were added, and the mixture was heated to reflux for 1 hour. After cooling the mixture to room temperature, it was allowed to stand, the supernatant was separated by decantation, and the solvent was distilled off under reduced pressure. The concentrated residue was combined with the solid portion remaining after decantation, ethyl acetate and water were added, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 2/1) to obtain the title compound (20.6 g, yield: 95%) as a yellow transparent oil. The NMR and ESI/MS data for this compound-are shown below. the mixture was heated to reflux for 1 hour the supernatant was separated by decantation the solvent was distilled off under reduced pressure were added extraction The organic layer was washed with water and saturated brine dried over anhydrous magnesium sulfate After filtering off the magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate 2/1)