diazinane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.8 g of the resulting 2-chloro-4-fluoro-5-isothiocyanatothiobenzoic acid (methoxycarbonylmethyl) ester in 50 ml of toluene is added dropwise, with stirring, at from 20° to 250° C. to a solution of 1.4 g of hexahydropyridazine in 20 ml of toluene. The batch is then stirred for a further 8 hours at room temperature and is then concentrated by evaporation in vacuo to yield 4.4 g of 2-chloro-4-fluoro-5-(1-hexahydropyridazinylthiocarbonylamino)-thiobenzoic acid (methoxycarbonylmethyl) ester in resinous form. is then concentrated by evaporation in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution containing 1,1′carbonyl diimidazole (0.893 g, 5.5 mmol) in 5 ml CH2Cl2 was added slowly to a solution of CH2Cl2 containing phenylbutyl alcohol (0.89 ml, 5.77 mmol). After stirring at room temperature for 1 hour, this solution was then added slowly to a solution containing perhydropyridazine mentioned above. The reaction was allowed to stir for overnight. The crude mixture was then concentrated and used without further purification. this solution was then added slowly to a solution to stir for overnight The crude mixture was then concentrated used without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.8 g of 2-chloro-4-fluoro-5-isothiocyanato-thiolbenzoic acid (methoxycarbonylmethyl) ester obtained in accordance with Example P3 in 50 ml of toluene is added dropwise, with stirring, at 20°-25° C. to a solution of 1.4 g of hexahydropyridazine in 20 ml of toluene. Stirring is continued for a further 8 hours at room temperature. Concentration by evaporation in vacuo yields 4.4 g of 2-chloro-4-fluoro-5-(1-hexahydropyridazinyl-thiocarbonylamino)-thiolbenzoic acid (methoxycarbonylmethyl) ester in resinous form. is added dropwise Concentration by evaporation in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.8 g of 2-chloro-4-fluoro-5-isothiocyanato-thiolbenzoic acid (methoxycarbonylmethyl) ester obtained in accordance with Example P3 in 50 ml of toluene is added dropwise, with stirring, at 20°-25° C. to a solution of 1.4 g of hexahydropyridazine in 20 ml of toluene. Stirring is continued for a further 8 hours at room temperature. Concentration by evaporation in vacuo yields 4.4 g of 2-chloro-4-fluoro-5-(1-hexahydropyridazinyl-thiocarbonylamino)-thiolbenzoic acid (methoxycarbonylmethyl) ester in resinous form. is added dropwise Concentration by evaporation in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reactor was charged with 0.0675 g of 5% palladium/carbon and 3.9 g of methanol, hydrogen substitution was carried out, and the catalyst was activated. Then, 2.8 g of a tetrahydropyridazine methanol solution [composition: tetrahydropyridazine 23.77% by weight, 0.67 g (0.008 mole), pyrrolidine 1.61% by weight, 0.05 g (0.0006 mole), 1-aminopyrrolidine 1.36% by weight, 0.04 g (0.0004 mole)] was added to adjust it to a 10% by weight methanol solution of tetrahydropyridazine. Thereafter, at room temperature, a catalytic hydrogenation reaction was carried out under a normal pressure for 5 days. After the reaction, the reaction solution was analyzed by GC. The results were as follows: Hexahydropyridazine 46.98%, tetrahydropyridazine 22.84%, 1-aminopyrrolidine 23.89%, and pyrrolidine 3.91%, and the formation of hexahydropyridazine as the intended product was confirmed. The reaction selectivity was hexahydropyridazine 60.89%, 1-aminopyrrolidine 30.96%, and the conversion of tetrahydropyridazine was 77.16%. Incidentally, 1-aminopyrrolizine was formed from tetrahydropyridazine by a reduction side reaction, and the formation of pyrrolidine as a decomposition product was recognized. Thereafter, at room temperature, a catalytic hydrogenation reaction After the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reactor was charged with 0.0675 g of 5% palladium/carbon and 3.9 g of methanol, hydrogen substitution was carried out, and the catalyst was activated. Then, 2.8 g of a tetrahydropyridazine methanol solution [composition: tetrahydropyridazine 23.77% by weight, 0.67 g (0.008 mole), pyrrolidine 1.61% by weight, 0.05 g (0.0006 mole), 1-aminopyrrolidine 1.36% by weight, 0.04 g (0.0004 mole)] was added to adjust it to a 10% by weight methanol solution of tetrahydropyridazine. Thereafter, at room temperature, a catalytic hydrogenation reaction was carried out under a normal pressure for 5 days. After the reaction, the reaction solution was analyzed by GC. The results were as follows: Hexahydropyridazine 46.98%, tetrahydropyridazine 22.84%, 1-aminopyrrolidine 23.89%, and pyrrolidine 3.91%, and the formation of hexahydropyridazine as the intended product was confirmed. The reaction selectivity was hexahydropyridazine 60.89%, 1-aminopyrrolidine 30.96%, and the conversion of tetrahydropyridazine was 77.16%. Incidentally, 1-aminopyrrolizine was formed from tetrahydropyridazine by a reduction side reaction, and the formation of pyrrolidine as a decomposition product was recognized. Thereafter, at room temperature, a catalytic hydrogenation reaction After the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.8 g of 2-chloro-4-fluoro-5-isothiocyanato-thiolbenzoic acid (methoxycarbonylmethyl) ester obtained in accordance with Example P3 in 50 ml of toluene is added dropwise, with stirring, at 20°-25° C. to a solution of 1.4 g of hexahydropyridazine in 20 ml of toluene. Stirring is continued for a further 8 hours at room temperature. Concentration by evaporation in vacuo yields 4.4 g of 2-chloro-4-fluoro-5-(1-hexahydropyridazinyl-thiocarbonylamino)-thiolbenzoic acid (methoxycarbonylmethyl) ester in resinous form. is added dropwise Concentration by evaporation in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reactor was charged with 0.0675 g of 5% palladium/carbon and 3.9 g of methanol, hydrogen substitution was carried out, and the catalyst was activated. Then, 2.8 g of a tetrahydropyridazine methanol solution [composition: tetrahydropyridazine 23.77% by weight, 0.67 g (0.008 mole), pyrrolidine 1.61% by weight, 0.05 g (0.0006 mole), 1-aminopyrrolidine 1.36% by weight, 0.04 g (0.0004 mole)] was added to adjust it to a 10% by weight methanol solution of tetrahydropyridazine. Thereafter, at room temperature, a catalytic hydrogenation reaction was carried out under a normal pressure for 5 days. After the reaction, the reaction solution was analyzed by GC. The results were as follows: Hexahydropyridazine 46.98%, tetrahydropyridazine 22.84%, 1-aminopyrrolidine 23.89%, and pyrrolidine 3.91%, and the formation of hexahydropyridazine as the intended product was confirmed. The reaction selectivity was hexahydropyridazine 60.89%, 1-aminopyrrolidine 30.96%, and the conversion of tetrahydropyridazine was 77.16%. Incidentally, 1-aminopyrrolizine was formed from tetrahydropyridazine by a reduction side reaction, and the formation of pyrrolidine as a decomposition product was recognized. Thereafter, at room temperature, a catalytic hydrogenation reaction After the reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-chloro-2-nitroaniline (2.36 g, 13.6 mmol), the hydrochloride salt of the hexahydro-pyridazine (5.0 g, 41 mmol) and anhydrous potassium carbonate (11.3 g, 82 mmol) in N,N-dimethylacetamide (20 ml) was stirred at 115-120° C. under nitrogen for 3 days. A sample was analyzed by NMR showed complete conversion of the starting material. The resultant mixture was cooled to room temperature, poured onto cold water (200 mL), stirred vigorously and incubated at 4° C. overnight. The resulting brown precipitate was collected by filtration, washed well with water and dried on the filter funnel. This was then slurried in diethyl ether, filtered, washed with additional diethyl ether, dried to afford 2-Nitro-5-(tetrahydro-pyridazin-1-yl)-phenylamine (1.9 g, 62.5%). The crude product was used in the next step without further purification. The resulting brown precipitate was collected by filtration washed well with water dried on the filter funnel filtered washed with additional diethyl ether dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4.8 g of the resulting 2-chloro-4-fluoro-5-isothiocyanatothiobenzoic acid (methoxycarbonylmethyl) ester in 50 ml of toluene is added dropwise, with stirring, at from 20° to 250° C. to a solution of 1.4 g of hexahydropyridazine in 20 ml of toluene. The batch is then stirred for a further 8 hours at room temperature and is then concentrated by evaporation in vacuo to yield 4.4 g of 2-chloro-4-fluoro-5-(1-hexahydropyridazinylthiocarbonylamino)-thiobenzoic acid (methoxycarbonylmethyl) ester in resinous form. is then concentrated by evaporation in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution containing 1,1′carbonyl diimidazole (0.893 g, 5.5 mmol) in 5 ml CH2Cl2 was added slowly to a solution of CH2Cl2 containing phenylbutyl alcohol (0.89 ml, 5.77 mmol). After stirring at room temperature for 1 hour, this solution was then added slowly to a solution containing perhydropyridazine mentioned above. The reaction was allowed to stir for overnight. The crude mixture was then concentrated and used without further purification. this solution was then added slowly to a solution to stir for overnight The crude mixture was then concentrated used without further purification