2-[benzyl(methyl)amino]ethyl 3-oxobutanoate

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

Procedure: A mixture of 4.0 g (16 mmol) of 2-(N-benzyl-N-methylamino)ethyl acetoacetate, 4.6 g (16 mmol) of cyclopropylmethyl 2-(3-nitrobenzylidene)acetoacetate, 1.12 ml of 28% aqueous ammonia and 40 ml of ethanol was stirred at the reflux temperature for 8 hours, and then the solvent was removed under reduced pressure. The residue was chromatographed on silica gel column to afford 3-cyclopropylmethyl 5-[2-(N-benzyl-N-methylamino)ethyl] 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate (3.5 g, 42.1%) as yellow oil. Treatment of this oil with hydrochloric acid gave the corresponding salt. the solvent was removed under reduced pressure The residue was chromatographed on silica gel column

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

Procedure: A mixture of 170 mg of 2-fluoro-5-nitrobenzaldehyde, 126 mg of methyl 3-aminocrotonate and 253 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 1 ml of 2-propanol was reacted and then purified in the same way as in Example 9 to yield 200 mg of the desired compound (144). was reacted purified in the same way as in Example 9

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

Procedure: A mixture of 556 mg of 3-chloro-2-nitrobenzaldehyde, 362 mg of methyl 3-aminocrotonate and 820 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 4 ml of 2-propanol was refluxed for 6 hours, and then the solvent was distilled off under reduced pressure. The residue was purified by a method of column chromatography onon silica gel to yield 900 mg of the desired compound (108). was refluxed for 6 hours the solvent was distilled off under reduced pressure The residue was purified by a method of column chromatography onon silica gel

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

Procedure: A mixture of 556 mg of 3-chloro-2-nitrobenzaldehyde, 362 mg of methyl 3-aminocrotonate and 820 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 4 ml of 2-propanol was refluxed for 6 hours, and then the solvent was distilled off under reduced pressure. The residue was purified by a method of column chromatography onon silica gel to yield 900 mg of the desired compound (108). was refluxed for 6 hours the solvent was distilled off under reduced pressure The residue was purified by a method of column chromatography onon silica gel

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

Procedure: A mixture of 320 mg of 3-chloro-2-fluorobenzaldehyde, 252 mg of methyl 3-aminocrotonate and 510 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 2 ml of 2-propanol was refluxed for 6 hours, and then the solvent was distilled off in vacuo. The residue was purified by the methods of a column chromatography on silica gel to yield 500 mg of the desired compound (106) was refluxed for 6 hours the solvent was distilled off in vacuo The residue was purified by the methods of a column chromatography on silica gel

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

Procedure: A mixture of 330 mg of 2-fluoro-3-nitrobenzaldehyde, 252 mg of methyl 3-aminocrotonate and 506 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 2 ml of 2-propanol was refluxed for 12 hours, and then the solvent was distilled off in vacuo. The residue was purified by the method of a column chromatography on silica gel to provide 492 mg of the desired compound (104). was refluxed for 12 hours the solvent was distilled off in vacuo The residue was purified by the method of a column chromatography on silica gel

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

Procedure: A mixture of 330 mg of 2-fluoro-3-nitrobenzaldehyde, 252 mg of methyl 3-aminocrotonate and 506 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 2 ml of 2-propanol was refluxed for 12 hours, and then the solvent was distilled off in vacuo. The residue was purified by the method of a column chromatography on silica gel to provide 492 mg of the desired compound (104). was refluxed for 12 hours the solvent was distilled off in vacuo The residue was purified by the method of a column chromatography on silica gel

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

Procedure: To a solution of 350 mg of 2,3-dichlorobenzaldehyde in 2 ml of 2-prapanol were added 510 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate and 250 mg of methyl 3-aminocrotonate. The mixture was refluxed for 12 hours. The solvent was distilled off in vacuo, and then the residue was chromatographed over silica gel with a mixture of chloroform and ethyl acetate as eluting solvents to yield 600 mg of the desired compound. The physical properties are as follows. The mixture was refluxed for 12 hours The solvent was distilled off in vacuo the residue was chromatographed over silica gel with a mixture of chloroform and ethyl acetate as eluting solvents

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

Procedure: A mixture of 15.2 g. of 1-benzyl-3-oxo-5-hydroxy-1,2,3,6-tetrahydropyridine, 13.1 g. of o-trifluoromethylbenzaldehyde, 18.7 g. of 2-(N-benzyl-N-methylamino)ethyl acetoacetate, 6 ml. of 28% ammonium hydroxide and 200 ml. of isopropanol was heated at reflux for 3 hours. The solution was evaporated to dryness. The residue was dissolved in 100 ml. of methylenechloride and extracted with 150 ml. of 15% hydrochloric acid. The acid extract was cooled and made basic with saturated sodium carbonate solution. The mixture was extracted with methylenechloride. The methylenechloride solution was dried over magnesium sulfate, then evaporated in vacuo to a solid residue. The residue was recrystallized from ethanol to obtain the title compound, m.p. 183°-185° C. A mixture of 15.2 g at reflux for 3 hours The solution was evaporated to dryness The residue was dissolved in 100 ml of methylenechloride and extracted with 150 ml The acid extract was cooled The mixture was extracted with methylenechloride The methylenechloride solution was dried over magnesium sulfate evaporated in vacuo to a solid residue The residue was recrystallized from ethanol

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

Procedure: A mixture of 4.0 g (16 mmol) of 2-(N-benzyl-N-methylamino)ethyl acetoacetate, 4.6 g (16 mmol) of cyclopropylmethyl 2-(3-nitrobenzylidene)acetoacetate, 1.12 ml of 28% aqueous ammonia and 40 ml of ethanol was stirred at the reflux temperature for 8 hours, and then the solvent was removed under reduced pressure. The residue was chromatographed on silica gel column to afford 3-cyclopropylmethyl 5-[2-(N-benzyl-N-methylamino)ethyl] 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate (3.5 g, 42.1%) as yellow oil. Treatment of this oil with hydrochloric acid gave the corresponding salt. the solvent was removed under reduced pressure The residue was chromatographed on silica gel column

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

Procedure: A mixture of 170 mg of 2-fluoro-5-nitrobenzaldehyde, 126 mg of methyl 3-aminocrotonate and 253 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 1 ml of 2-propanol was reacted and then purified in the same way as in Example 9 to yield 200 mg of the desired compound (144). was reacted purified in the same way as in Example 9

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

Procedure: A mixture of 556 mg of 3-chloro-2-nitrobenzaldehyde, 362 mg of methyl 3-aminocrotonate and 820 mg of 2-(N-benzyl-N-methylamino)ethyl acetoacetate in 4 ml of 2-propanol was refluxed for 6 hours, and then the solvent was distilled off under reduced pressure. The residue was purified by a method of column chromatography onon silica gel to yield 900 mg of the desired compound (108). was refluxed for 6 hours the solvent was distilled off under reduced pressure The residue was purified by a method of column chromatography onon silica gel