ethyl 5-chloro-5-oxopentanoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 150 mg of ethyl {[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]amino}acetate was dissolved in 3.0 ml of THF, and 0.060 ml of triethylamine and 0.060 ml of ethyl 5-chloro-5-oxopentanoate were added, followed by overnight stirring at room temperature. Water was added to the reaction mixture, followed by extraction with chloroform. The resulting organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and then concentrated under a reduced pressure. By purifying the resulting residue by silica gel column chromatography, 199 mg of ethyl 5-[[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl](2-ethoxy-2-oxoethyl)amino]-5-oxopentanoate was obtained. followed by extraction with chloroform The resulting organic layer was washed with aqueous saturated sodium chloride dried over anhydrous sodium sulfate concentrated under a reduced pressure By purifying the resulting residue by silica gel column chromatography

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

Procedure: A solution of ethyl 4-(chloroformyl)butyrate (0.714 g, 0.004 mol) in dichloromethane (5 ml) was added dropwise to a stirred solution of 1-[2-amino-3-[(4-methoxyphenyl)methoxy]propyl]-1H-imidazole (Example 32c; 1.0 g, 0.0038 mol) and triethylamine (0.4 g, 0.004 mol) in dichloromethane (20 ml) at room temperature. The solution was stirred for 12 hours, washed with an aqueous saturated solution of ammonium chloride and dried (Na2SO4). The solvent was evaporated off under reduced pressure and the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform) to give ethyl 5-[[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl]ethyl]amino]-5-oxopentanoate as a pale-yellow oil. washed with an aqueous saturated solution of ammonium chloride dried (Na2SO4) The solvent was evaporated off under reduced pressure the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform)

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

Procedure: A solution of ethyl 4-(chloroformyl)butyrate (0.714 g, 0.004 mol) in dichloromethane (5 ml) was added dropwise to a stirred solution of 1-[2-amino-3-[(4-methoxyphenyl)methoxy]propyl]-1H-imidazole (Example 32c; 1.0 g, 0.0038 mol) and triethylamine (0.4 g, 0.004 mol) in dichloromethane (20 ml) at room temperature. The solution was stirred for 12 hours, washed with an aqueous saturated solution of ammonium chloride and dried (Na2SO4). The solvent was evaporated off under reduced pressure and the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform) to give ethyl 5-[[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl]ethyl]amino]-5-oxopentanoate as a pale-yellow oil. washed with an aqueous saturated solution of ammonium chloride dried (Na2SO4) The solvent was evaporated off under reduced pressure the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform)

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

Procedure: 150 mg of ethyl {[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]amino}acetate was dissolved in 3.0 ml of THF, and 0.060 ml of triethylamine and 0.060 ml of ethyl 5-chloro-5-oxopentanoate were added, followed by overnight stirring at room temperature. Water was added to the reaction mixture, followed by extraction with chloroform. The resulting organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and then concentrated under a reduced pressure. By purifying the resulting residue by silica gel column chromatography, 199 mg of ethyl 5-[[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl](2-ethoxy-2-oxoethyl)amino]-5-oxopentanoate was obtained. followed by extraction with chloroform The resulting organic layer was washed with aqueous saturated sodium chloride dried over anhydrous sodium sulfate concentrated under a reduced pressure By purifying the resulting residue by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: By using 120 mg of 2-({3-[(cyclopropylamino)methyl]benzoyl}amino)-N-[4-(pyridin-4-ylmethyl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide and 120 mg of ethyl 5-chloro-5-oxopentanoate, the reaction similar to Preparation Example 13 was performed, thereby obtaining 105 mg of ethyl 5-(cyclopropyl {3-[(3-{[4-(pyridin-4-ylmethyl)phenyl]carbamoyl}-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)carbamoyl]benzyl}amino)-5-oxopentanoate. the reaction similar to Preparation Example 13

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

Procedure: A solution of ethyl 4-(chloroformyl)butyrate (0.714 g, 0.004 mol) in dichloromethane (5 ml) was added dropwise to a stirred solution of 1-[2-amino-3-[(4-methoxyphenyl)methoxy]propyl]-1H-imidazole (Example 32c; 1.0 g, 0.0038 mol) and triethylamine (0.4 g, 0.004 mol) in dichloromethane (20 ml) at room temperature. The solution was stirred for 12 hours, washed with an aqueous saturated solution of ammonium chloride and dried (Na2SO4). The solvent was evaporated off under reduced pressure and the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform) to give ethyl 5-[[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl]ethyl]amino]-5-oxopentanoate as a pale-yellow oil. washed with an aqueous saturated solution of ammonium chloride dried (Na2SO4) The solvent was evaporated off under reduced pressure the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform)

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

Procedure: 150 mg of ethyl {[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]amino}acetate was dissolved in 3.0 ml of THF, and 0.060 ml of triethylamine and 0.060 ml of ethyl 5-chloro-5-oxopentanoate were added, followed by overnight stirring at room temperature. Water was added to the reaction mixture, followed by extraction with chloroform. The resulting organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sulfate and then concentrated under a reduced pressure. By purifying the resulting residue by silica gel column chromatography, 199 mg of ethyl 5-[[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl](2-ethoxy-2-oxoethyl)amino]-5-oxopentanoate was obtained. followed by extraction with chloroform The resulting organic layer was washed with aqueous saturated sodium chloride dried over anhydrous sodium sulfate concentrated under a reduced pressure By purifying the resulting residue by silica gel column chromatography

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

Procedure: A solution of ethyl 4-(chloroformyl)butyrate (0.714 g, 0.004 mol) in dichloromethane (5 ml) was added dropwise to a stirred solution of 1-[2-amino-3-[(4-methoxyphenyl)methoxy]propyl]-1H-imidazole (Example 32c; 1.0 g, 0.0038 mol) and triethylamine (0.4 g, 0.004 mol) in dichloromethane (20 ml) at room temperature. The solution was stirred for 12 hours, washed with an aqueous saturated solution of ammonium chloride and dried (Na2SO4). The solvent was evaporated off under reduced pressure and the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform) to give ethyl 5-[[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl]ethyl]amino]-5-oxopentanoate as a pale-yellow oil. washed with an aqueous saturated solution of ammonium chloride dried (Na2SO4) The solvent was evaporated off under reduced pressure the crude product was purified by column chromatography (silica gel, 2% ethanol in chloroform)