O-propylhydroxylamine;hydrochloride

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

Procedure: 0.2 Gram of 2-propionyl-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione was dissolved in 10 ml of chloroform and 0.07 g of propoxyamine hydrochloride and 0.5 ml of pyridine were added to the resulting solution which was then stirred at 50°-60° C. for 5 hours. The reaction solution was poured into water, acidified with dilute hydrochloric acid and extracted with chloroform. After removing chloroform, the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1) to obtain 0.11 g of 2-(1-propoxyaminopropylidene)-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione. extracted with chloroform After removing chloroform the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1)

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

Procedure: 10.7 g (0.04 mol) of methyl 3-chlorocarbonyl-2,4-dichlorobenzoate in 100 ml of methylene chloride were slowly added dropwise at 30° C. to a solution of 4.50 g (0.04 mol) of propoxyamine hydrochloride and 4.05 g (0.04 mol) of triethylamine in 200 ml of methylene chloride. After the reaction mixture had been stirred for 2 hours at room temperature, it was washed with dilute phosphoric acid, dried and concentrated. The resulting residue was chromatographed on silica gel (eluent: toluene/ethyl acetate=9/1). This gave 11.50 g of methyl 2,4-dichloro-3-(N-propoxyamino)carbonylbenzoate. it was washed with dilute phosphoric acid dried concentrated The resulting residue was chromatographed on silica gel (eluent: toluene/ethyl acetate=9/1)

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

Procedure: 10.7 g (0.04 mol) of methyl 3-chlorocarbonyl-2,4-dichlorobenzoate in 100 ml of methylene chloride were slowly added dropwise at 30° C. to a solution of 4.50 g ((0.04 mol) of propoxyamine hydrochloride and 4.05 g (0.04 mol) of triethylamine in 200 ml of methylene chloride. After the reaction mixture had been stirred for 2 hours at room temperature, it was washed with dilute phosphoric acid, dried and concentrated. The residue obtained was chromatographed on silica gel (eluant:toluene/ethyl acetate=9/1). This gave 11.50 g of methyl 2,4-dichloro-3-propoxyaminocarbonylbenzoate. it was washed with dilute phosphoric acid dried concentrated The residue obtained was chromatographed on silica gel (eluant:toluene/ethyl acetate=9/1)

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

Procedure: To a solution of 113.2 g. of propoxyamine hydrochloride in 200 ml. of ice cold water there is added 81.2 g. of 50% aqueous sodium hydroxide solution. The mixture is stirred for thirty minutes and 141.0 g. of S-methyl-2-thiopseudourea sulfate and 200 ml. of water are added. The mixture is stirred at room temperature for two hours and then heated to reflux for one hour. The mixture is treated with 81.2 g. of 50% aqueous sodium hydroxide filtered and evaporated in vacuo. The residue is slurried in 200 ml. of absolute ethanol, the suspension filtered and the filtrate evaporated to an oil. The crude oil is dissolved in 300 ml. of chloroform, the mixture is cooled and filtered to give a clear solution of the guanidine free base. The chloroform solution is made acidic with methanolic hydrogen chloride and then evaporated in vacuo to give propoxyguanidine hydrochloride as a clear viscous oil (m.p. of picrate 179°-80° C.). of ice cold water there is added 81.2 g The mixture is stirred at room temperature for two hours heated to reflux for one hour The mixture is treated with 81.2 g of 50% aqueous sodium hydroxide filtered evaporated in vacuo of absolute ethanol, the suspension filtered the filtrate evaporated to an oil The crude oil is dissolved in 300 ml of chloroform, the mixture is cooled filtered

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

Procedure: (4)-(a) A mixture of S-methyl 2-(6-formamidopyridin-2-yl)thioglyoxylate (4.48 g.), methanol (20 ml.) and 1 N aqueous solution of sodium hydroxide (20 ml.) was stirred for 50 minutes at ambient temperature to give a solution containing 2-(6-formamidopyridin-2-yl)glyoxylic acid. To the solution was added O-propylhydroxylamine hydrochloride (2.23 g.), and the mixture was stirred for 35 minutes at the same temperature. The reaction mixture was adjusted to pH 7 with hydrochloric acid and the methanol was distilled off. The remaining aqueous mixture was washed with ethyl acetate, and ethyl acetate was added thereto and then adjusted to pH 1 with 10% hydrochloric acid. The ethyl acetate layer was separated, washed with water, dried over magnesium sulfate, treated with activated charcoal and then the solvent was distilled off. Thus obtained product was washed with a mixture of diethyl ether and diisopropyl ether and then dried to give 2-(6-formamidopyridin-2-yl)-2-propoxyiminoacetic acid (syn isomer) (1.76 g.), mp. 140° to 142° C. (dec.). to give a solution the mixture was stirred for 35 minutes at the same temperature the methanol was distilled off The remaining aqueous mixture was washed with ethyl acetate, and ethyl acetate was added The ethyl acetate layer was separated washed with water dried over magnesium sulfate treated with activated charcoal the solvent was distilled off Thus obtained product was washed with a mixture of diethyl ether and diisopropyl ether dried

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

Procedure: (4)-(a) A mixture of S-methyl 2-(6-formamidopyridin-2-yl)thioglyoxylate (4.48 g.), methanol (20 ml.) and 1 N aqueous solution of sodium hydroxide (20 ml.) was stirred for 50 minutes at ambient temperature to give a solution containing 2-(6-formamidopyridin-2-yl)glyoxylic acid. To the solution was added O-propylhydroxylamine hydrochloride (2.23 g.), and the mixture was stirred for 35 minutes at the same temperature. The reaction mixture was adjusted to pH 7 with hydrochloric acid and the methanol was distilled off. The remaining aqueous mixture was washed with ethyl acetate, and ethyl acetate was added thereto and then adjusted to pH 1 with 10% hydrochloric acid. The ethyl acetate layer was separated, washed with water, dried over magnesium sulfate, treated with activated charcoal and then the solvent was distilled off. Thus obtained product was washed with a mixture of diethyl ether and diisopropyl ether and then dried to give 2-(6-formamidopyridin-2-yl)-2-propoxyiminoacetic acid (syn isomer) (1.76 g.), mp. 140° to 142° C. (dec.). to give a solution the mixture was stirred for 35 minutes at the same temperature the methanol was distilled off The remaining aqueous mixture was washed with ethyl acetate, and ethyl acetate was added The ethyl acetate layer was separated washed with water dried over magnesium sulfate treated with activated charcoal the solvent was distilled off Thus obtained product was washed with a mixture of diethyl ether and diisopropyl ether dried

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

Procedure: 0.2 Gram of 2-propionyl-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione was dissolved in 10 ml of chloroform and 0.07 g of propoxyamine hydrochloride and 0.5 ml of pyridine were added to the resulting solution which was then stirred at 50°-60° C. for 5 hours. The reaction solution was poured into water, acidified with dilute hydrochloric acid and extracted with chloroform. After removing chloroform, the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1) to obtain 0.11 g of 2-(1-propoxyaminopropylidene)-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione. extracted with chloroform After removing chloroform the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1)

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

Procedure: 0.2 Gram of 2-propionyl-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione was dissolved in 10 ml of chloroform and 0.07 g of propoxyamine hydrochloride and 0.5 ml of pyridine were added to the resulting solution which was then stirred at 50°-60° C. for 5 hours. The reaction solution was poured into water, acidified with dilute hydrochloric acid and extracted with chloroform. After removing chloroform, the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1) to obtain 0.11 g of 2-(1-propoxyaminopropylidene)-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione. extracted with chloroform After removing chloroform the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1)

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

Procedure: 1-(Amino-oxy)-propane hydrochloride (32 mg, 0.29 mmol) was added to a solution of (E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (61.3 mg, 0.20 mmol) in a mixture methanol/dichloromethane (8:2, 3.5 mL) at room temperature. The reaction mixture was stirred overnight. After concentration to dryness, the residue was purified by chromatography on silica gel using dichloromethane/methanol (95:5) as eluent. The title product was obtained as a white solid (56.0 mg, 76%). After concentration to dryness the residue was purified by chromatography on silica gel

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

Procedure: 1-(Amino-oxy)-propane hydrochloride (32 mg, 0.29 mmol) was added to a solution of (E)-6-(3-(3-acetylazetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (61.3 mg, 0.20 mmol) in a mixture methanol/dichloromethane (8:2, 3.5 mL) at room temperature. The reaction mixture was stirred overnight. After concentration to dryness, the residue was purified by chromatography on silica gel using dichloromethane/methanol (95:5) as eluent. The title product was obtained as a white solid (56.0 mg, 76%). After concentration to dryness the residue was purified by chromatography on silica gel

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

Procedure: 0.2 Gram of 2-propionyl-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione was dissolved in 10 ml of chloroform and 0.07 g of propoxyamine hydrochloride and 0.5 ml of pyridine were added to the resulting solution which was then stirred at 50°-60° C. for 5 hours. The reaction solution was poured into water, acidified with dilute hydrochloric acid and extracted with chloroform. After removing chloroform, the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1) to obtain 0.11 g of 2-(1-propoxyaminopropylidene)-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione. extracted with chloroform After removing chloroform the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1)

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

Procedure: 0.2 Gram of 2-propionyl-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione was dissolved in 10 ml of chloroform and 0.07 g of propoxyamine hydrochloride and 0.5 ml of pyridine were added to the resulting solution which was then stirred at 50°-60° C. for 5 hours. The reaction solution was poured into water, acidified with dilute hydrochloric acid and extracted with chloroform. After removing chloroform, the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1) to obtain 0.11 g of 2-(1-propoxyaminopropylidene)-5-[2-(4-trifluoromethylphenylthio)ethyl]cyclohexane-1,3-dione. extracted with chloroform After removing chloroform the residue was purified by thin layer chromatography (eluent, hexane:ethyl acetate=5:1)