2-chloroethylsulfanylcyclohexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.06 g of 2-chloroethyl cyclohexyl sulfide in 50 cm3 of acetonitrile, followed by 1.78 g of potassium iodide and 7.25 g of potassium carbonate, were added with stirring, at a temperature in the region of 20° C. and under an inert atmosphere, to a solution of 3.9 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate in 50 cm3 of acetonitrile. The mixture was heated for 18 hours at a temperature in the region of 80° C. After cooling to approximately 20° C., the mixture had 100 cm3 of water and 100 cm3 of ethyl acetate added. The organic phase was separated by settling, while the aqueous phase was extracted with 200 cm3 of ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 45° C. An oil was obtained, which product was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μ; diameter 3.5 cm; height 46 cm), elution was carried out with. a dichloromethane/methanol (95/5 by volume) mixture, and 50-cm3 fractions were collected. Fractions 18 to 37 were combined and concentrated as above. A product was obtained, which product was purified a second time by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μ; diameter 4 cm; height 40 cm), elution was carried out with an ethyl acetate/cyclohexane (7/3 by volume) mixture, and 100-cm3 fractions were collected. Fractions 24 to 54 were combined and then concentrated under the same conditions as above. 3.7 g of methyl (3R,4R)-1-[2-(cyclohexylthio)ethyl]-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate were obtained in the form of an oil with a brown color. were added After cooling to approximately 20° C. added The organic phase was separated was extracted with 200 cm3 of ethyl acetate dried over sodium sulfate filtered concentrated under reduced pressure (5 kPa) at a temperature in the region of 45° C An oil was obtained which product was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μ; diameter 3.5 cm; height 46 cm), elution a dichloromethane/methanol (95/5 by volume) mixture, and 50-cm3 fractions were collected concentrated as above A product was obtained which product was purified a second time by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μ; diameter 4 cm; height 40 cm), elution were collected concentrated under the same conditions as above

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

Procedure: A stirred mixture of 0.54 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate, 0.295 g of 2-chloroethyl cyclohexyl sulfide, 0.23 g of potassium carbonate, and 0.27 g of potassium iodide in 9 cm3 of acetonitrile and 1 cm3 of methanol was brought to a temperature in the region of the boiling point under an inert atmosphere for 20 hours. The reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under an argon pressure of 80 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution was carried out with a dichloromethane/methanol (95/5 by volume) mixture, and 35-cm3 fractions were collected. Fractions 23 to 40 were combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.4 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclohexylthio)ethyl]piperidine-3-carboxylate was obtained in the form of a lacquer with a brown color. The reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C The residue obtained was purified by chromatography under an argon pressure of 80 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution were collected concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.32 g of ethyl 1-(2-cyclohexylethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained. After cooling to about 20° C. the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g) eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume) The fractions containing the product concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C