4-methyloxane-2,6-dione

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:

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

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

Procedure: 1.6 g of 3-methylglutaric anhydride and then 1.48 cm3 of N-methylpiperazine are added to 20 cm3 of dioxane. After stirring for 4 hours, an additional 320 mg of 3-methylglutaric anhydride are added. The stirring is continued at 20° C. for 18 hours. The solvent is evaporated under reduced pressure (2.7 kPa), at 50° C. The resulting oil is dried at 50° C. (90 Pa) to give 3.1 g of (3RS)-3-methyl-5-(4-methylpiperazin-1-yl)-5-oxopentanoic acid in the form of a yellow lacquer which is used as it is. The stirring is continued at 20° C. for 18 hours The solvent is evaporated under reduced pressure (2.7 kPa), at 50° C The resulting oil is dried at 50° C. (90 Pa)

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

Procedure: 1.6 g of 3-methylglutaric anhydride and then 2.62 g of piperazin-1-ylcarboxymethylpyrrolidine are added to 20 cm3 of dioxane. After stirring for 8 hours, an additional 320 mg of 3-methylglutaric anhydride are added and then the stirring is continued at 20° C. for 18 hours. The solvent is evaporated under reduced pressure and then the resulting oil is dried at 45° C. (90 Pa) to give 4.5 g of 5-(4-methylpiperazin-1-yl)-5-oxopentanoic acid in the form of an orange-colored oil which is used as it is. the stirring is continued at 20° C. for 18 hours The solvent is evaporated under reduced pressure the resulting oil is dried at 45° C. (90 Pa)

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

Procedure: 1.6 g of 3-methylglutaric anhydride and then 2.62 g of pyrrolidinocarbonylmethyl-piperazine are added to 10 cm3 of dioxane. After stirring for 8 hours, an additional 320 mg of 3-methylglutaric anhydride are added and then the stirring is continued at 20° C. for 18 hours. The solvent is then evaporated under reduced pressure and then the resulting oil is dried at 45° C. (90 Pa) to give 4.5 g of (3RS)-3-methyl-5-oxo-5-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pentanoic acid in the form of an orange-colored oil which is used as it is. the stirring is continued at 20° C. for 18 hours The solvent is then evaporated under reduced pressure the resulting oil is dried at 45° C. (90 Pa)

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

Procedure: Compounds of Examples 57 to 65 were prepared in the same manner as in Example 56 except that (1RS, 2RS)-2-(4-biphenylyl)-1-methyl-3-(2-naphthyl)propylamine and/or 3-methylglutaric anhydride used as the starting materials in the above reaction were changed to the corresponding amine compounds and/or acid anhydrides. used as the starting materials in the above reaction

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

Procedure: A mixture of triclosan (22.3 g.), 3-methylglutaric anhydride (15.0 g.) and triethylamine (15 ml.) in ether (250 ml.) was stirred for 20 hours, and then washed first with 2M hydrochloric acid (50 ml.) and then with water (3×150 ml.). The ether phase was dried (MgSO4) and evaporated. A portion (20 g.) of the residual oil was purified by chromatography on silica gel using methylene chloride as eluant to give (D) as a colourless oil (7.4 g.) ; NMR (CDCl3): 0.8-1.3 (3H,d, CH3), 2.1-2.8 (5H,m,CH2CO+CH3CH), 6.7-7.6 (6H, m, aromatic H), 11.25 (1H,s, CO2H)ppm. washed first with 2M hydrochloric acid (50 ml.) The ether phase was dried (MgSO4) evaporated A portion (20 g.) of the residual oil was purified by chromatography on silica gel

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

Procedure: A mixture of triclosan (22.3 g.), 3-methylglutaric anhydride (15.0 g.) and triethylamine (15 ml.) in ether (250 ml.) was stirred for 20 hours, and then washed first with 2M hydrochloric acid (50 ml.) and then with water (3×150 ml.). The ether phase was dried (MgSO4) and evaporated. A portion (20 g.) of the residual oil was purified by chromatography on silica gel using methylene chloride as eluant to give (D) as a colourless oil (7.4 g.) ; NMR (CDCl3): 0.8-1.3 (3H,d, CH3), 2.1-2.8 (5H,m,CH2CO+CH3CH), 6.7-7.6 (6H, m, aromatic H), 11.25 (1H,s, CO2H)ppm. washed first with 2M hydrochloric acid (50 ml.) The ether phase was dried (MgSO4) evaporated A portion (20 g.) of the residual oil was purified by chromatography on silica gel

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]benzyl amine (2.32 g, 6.84 mmol; prepared as described in Example 7), 3-methylglutaric anhydride (0.88 g, 6.84 mmol), and THF (20 mL) was stirred at room temperature for 3 h and then concentrated to an oily residue. This material was dissolved in acetic anhydride (25 mL), heated at 100° C. for 4 h, cooled, and added slowly to saturated aqueous NaHCO3. Extraction with CH2Cl2, separation of the organic layer, drying, filtration and evaporation afforded an oil. This material was chromatographed on flash grade silica using 97:3/CH2Cl2 :MeOH to give 4-methyl-1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidine-2,6-dione as an oil. This was dissolved in ether and added to ethereal HCl causing a solid to form. Filtration afforded 4-methyl-1-[[3-[[ 1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidine-2,6-dione dihydrochloride (1.43 g, 40%), m.p. 196°-200° C. H-1 NMR and mass spectral analysis supported the assigned structure. concentrated to an oily residue This material was dissolved in acetic anhydride (25 mL) cooled added slowly to saturated aqueous NaHCO3 Extraction with CH2Cl2, separation of the organic layer drying filtration and evaporation afforded an oil This material was chromatographed on flash grade silica using 97:3/CH2Cl2