4-butyl-1,2-diphenylpyrazolidine-3,5-dione

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: Then, p-Toluenesulfonyl chloride (0.95 g, 5.0 mmole) was allowed to react with a dimethylformamide (20 ml) suspension of the Thallium (I) salt of phenylbutazone. Within a few minutes the solvent became pink and a yellow solid, instead of the white Thallium (I) salt of phenylbutazone, was observed suspended in the pink solution. The suspension was stirred overnight in a tightly sealed flask, then it was diluted with 100 ml of ether and filtered. The filtrate was concentrated in vacuo to remove the ether and the dimethylformamide was evaporated under a stream of nitrogen. The residue from the evaporation was suspended in dichloromethane and filtered. Analysis of the filtrate by TLC showed that it contained only one major component. The dichloromethane was evaporated in vacuo and the residue was crystallized from ether to give 0.76 g (mp 112°-121° C., 33% yield) of yellow crystals which contained only one components by TLC analysis. Recrystallization of the yellow crystals gave analytically pure crystals, mp 125°-127° C. with spectral properties identical to the crystals, mp 112°-121° C. Within a few minutes the solvent became pink filtered The filtrate was concentrated in vacuo to remove the ether the dimethylformamide was evaporated under a stream of nitrogen The residue from the evaporation filtered The dichloromethane was evaporated in vacuo the residue was crystallized from ether

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

実験手順: Then, p-Toluenesulfonyl chloride (0.95 g, 5.0 mmole) was allowed to react with a dimethylformamide (20 ml) suspension of the Thallium (I) salt of phenylbutazone. Within a few minutes the solvent became pink and a yellow solid, instead of the white Thallium (I) salt of phenylbutazone, was observed suspended in the pink solution. The suspension was stirred overnight in a tightly sealed flask, then it was diluted with 100 ml of ether and filtered. The filtrate was concentrated in vacuo to remove the ether and the dimethylformamide was evaporated under a stream of nitrogen. The residue from the evaporation was suspended in dichloromethane and filtered. Analysis of the filtrate by TLC showed that it contained only one major component. The dichloromethane was evaporated in vacuo and the residue was crystallized from ether to give 0.76 g (mp 112°-121° C., 33% yield) of yellow crystals which contained only one components by TLC analysis. Recrystallization of the yellow crystals gave analytically pure crystals, mp 125°-127° C. with spectral properties identical to the crystals, mp 112°-121° C. Within a few minutes the solvent became pink filtered The filtrate was concentrated in vacuo to remove the ether the dimethylformamide was evaporated under a stream of nitrogen The residue from the evaporation filtered The dichloromethane was evaporated in vacuo the residue was crystallized from ether

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

実験手順: Potassium carbonate (2.26 g, 0.016 mole) was suspended in an acetone (125 ml) solution of phenylbutazone and the suspension was refluxed overnight. The next day pivalyloxymethyl chloride (4.99 g, 0.033 mole) was added to the resulting solution and the solution was refluxed overnight. The suspension was cooled and filtered; the residue (2.00 g, 83%) was potassium chloride. The filtrate was concentrated in vacuo and the residue was suspended in ether, then filtered. The residue was washed with ether until the washings did not contain any product by TLC. The residue from the ether suspension was the potassium salt of phenylbutazone (2.25 g, 20%). The ether was then concentrated in vacuo and the residue was absorbed on silica gel and chromatographed on neutral silica gel (CC-7, Mallinckrodt) using petroleum ether bp 30°-60° C. -- ether (1:1) as the eluent to give two fractions. The first fraction (Rf 0.46, silica gel, heptane-ether, 1:1 was crystallized from heptane-petroleum ether bp 30-60° C., 1:1 to give 0.63 g (mp 116°-117° C., 5% yield) of 1,2-diphenyl-4-butyl-4-pivalyloxymethyl-3,5-pyrazolidinedione. nmr (CDCl3) δ 4.40 (S, 2, ##STR10## the suspension was refluxed overnight the solution was refluxed overnight The suspension was cooled filtered The filtrate was concentrated in vacuo filtered The residue was washed with ether until the washings The ether was then concentrated in vacuo the residue was absorbed on silica gel chromatographed on neutral silica gel (CC-7, Mallinckrodt) ether (1:1) as the eluent to give two fractions The first fraction (Rf 0.46, silica gel, heptane-ether, 1:1 was crystallized from heptane-petroleum ether bp 30-60° C., 1:1

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

実験手順: Potassium carbonate (2.26 g, 0.016 mole) was suspended in an acetone (125 ml) solution of phenylbutazone and the suspension was refluxed overnight. The next day pivalyloxymethyl chloride (4.99 g, 0.033 mole) was added to the resulting solution and the solution was refluxed overnight. The suspension was cooled and filtered; the residue (2.00 g, 83%) was potassium chloride. The filtrate was concentrated in vacuo and the residue was suspended in ether, then filtered. The residue was washed with ether until the washings did not contain any product by TLC. The residue from the ether suspension was the potassium salt of phenylbutazone (2.25 g, 20%). The ether was then concentrated in vacuo and the residue was absorbed on silica gel and chromatographed on neutral silica gel (CC-7, Mallinckrodt) using petroleum ether bp 30°-60° C. -- ether (1:1) as the eluent to give two fractions. The first fraction (Rf 0.46, silica gel, heptane-ether, 1:1 was crystallized from heptane-petroleum ether bp 30-60° C., 1:1 to give 0.63 g (mp 116°-117° C., 5% yield) of 1,2-diphenyl-4-butyl-4-pivalyloxymethyl-3,5-pyrazolidinedione. nmr (CDCl3) δ 4.40 (S, 2, ##STR10## the suspension was refluxed overnight the solution was refluxed overnight The suspension was cooled filtered The filtrate was concentrated in vacuo filtered The residue was washed with ether until the washings The ether was then concentrated in vacuo the residue was absorbed on silica gel chromatographed on neutral silica gel (CC-7, Mallinckrodt) ether (1:1) as the eluent to give two fractions The first fraction (Rf 0.46, silica gel, heptane-ether, 1:1 was crystallized from heptane-petroleum ether bp 30-60° C., 1:1

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

実験手順: Then, p-Toluenesulfonyl chloride (0.95 g, 5.0 mmole) was allowed to react with a dimethylformamide (20 ml) suspension of the Thallium (I) salt of phenylbutazone. Within a few minutes the solvent became pink and a yellow solid, instead of the white Thallium (I) salt of phenylbutazone, was observed suspended in the pink solution. The suspension was stirred overnight in a tightly sealed flask, then it was diluted with 100 ml of ether and filtered. The filtrate was concentrated in vacuo to remove the ether and the dimethylformamide was evaporated under a stream of nitrogen. The residue from the evaporation was suspended in dichloromethane and filtered. Analysis of the filtrate by TLC showed that it contained only one major component. The dichloromethane was evaporated in vacuo and the residue was crystallized from ether to give 0.76 g (mp 112°-121° C, 33% yield) of yellow crystals which contained only one component by TLC analysis. Recrystallization of the yellow crystals gave analytically pure crystals, mp 125°-127° C with spectral properties identical to the crystals, mp 112°-121° C. Within a few minutes the solvent became pink filtered The filtrate was concentrated in vacuo to remove the ether the dimethylformamide was evaporated under a stream of nitrogen The residue from the evaporation filtered The dichloromethane was evaporated in vacuo the residue was crystallized from ether

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

実験手順: Then, p-Toluenesulfonyl chloride (0.95 g, 5.0 mmole) was allowed to react with a dimethylformamide (20 ml) suspension of the Thallium (I) salt of phenylbutazone. Within a few minutes the solvent became pink and a yellow solid, instead of the white Thallium (I) salt of phenylbutazone, was observed suspended in the pink solution. The suspension was stirred overnight in a tightly sealed flask, then it was diluted with 100 ml of ether and filtered. The filtrate was concentrated in vacuo to remove the ether and the dimethylformamide was evaporated under a stream of nitrogen. The residue from the evaporation was suspended in dichloromethane and filtered. Analysis of the filtrate by TLC showed that it contained only one major component. The dichloromethane was evaporated in vacuo and the residue was crystallized from ether to give 0.76 g (mp 112°-121° C, 33% yield) of yellow crystals which contained only one component by TLC analysis. Recrystallization of the yellow crystals gave analytically pure crystals, mp 125°-127° C with spectral properties identical to the crystals, mp 112°-121° C. Within a few minutes the solvent became pink filtered The filtrate was concentrated in vacuo to remove the ether the dimethylformamide was evaporated under a stream of nitrogen The residue from the evaporation filtered The dichloromethane was evaporated in vacuo the residue was crystallized from ether

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

実験手順: Potassium carbonate (2.26 g, 0.016 mole) was suspended in an acetone (125 ml) solution of phenylbutazone and the suspension was refluxed overnight. The next day pivalyloxymethyl chloride (4.99 g, 0.033 mole) was added to the resulting solution and the solution was refluxed overnight. The suspension was cooled and filtered; the residue (2.00 g, 83%) was potassium chloride. The filtrate was concentrated in vacuo and the residue was suspended in ether, then filtered. The residue was washed with ether until the washings did not contain any product by TLC. The residue from the ether suspension was the potassium salt of phenylbutazone (2.25 g, 20%). The ether was then concentrated in vacuo and the residue was absorbed on silica gel and chromatographed on neutral silica gel (CC-7, Mallinckrodt) using petroleum ether bp 30°-60° C -- ether (1:1) as the eluent to give two fractions. The first fraction (Rf 0.46, silica gel, heptane-ether, 1:1) was crystallized from heptane-petroleum ether bp 30°-60° C, 1:1 to give 0.63 g (mp 116°-117° C, 5% yield) of 1,2-diphenyl-4-butyl-4-pivalyloxymethyl-3,5-pyrazolidinedione. nmr (CDCl3) δ 4.40 ##EQU4## the suspension was refluxed overnight the solution was refluxed overnight The suspension was cooled filtered The filtrate was concentrated in vacuo filtered The residue was washed with ether until the washings The ether was then concentrated in vacuo the residue was absorbed on silica gel chromatographed on neutral silica gel (CC-7, Mallinckrodt) ether (1:1) as the eluent to give two fractions The first fraction (Rf 0.46, silica gel, heptane-ether, 1:1) was crystallized from heptane-petroleum ether bp 30°-60° C, 1:1

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

実験手順: Phenylbutazone (1,2-diphenyl-3,5-pyrazolidinedione; 11.00 g, 0.035 mole) was treated with 11.55 g (0.055 mole) of trifluoroacetic anhydride. The resulting solid suspension was shaken or mechanically stirred until a homogeneous solution was obtained, then it was stirred with a magnetic stirrer at room temperature in a tightly closed flask for one hour. The solution was concentrated in vacuo for one hour and the oily residue obtained was dissolved in 50 ml of acetone and allowed to react with 12.5 g (0.055 mole) of nicotinic anhydride. The initial suspension became homogeneous after 0.25 hours with concomitant formation of a yellow color. After an additional one hour at room temperature, the yellow solution was concentrated in vacuo and the residue was dissolved in 200 ml of dichloromethane. The dichloromethane solution was extracted first with an aqueous sodium bicarbonate solution (12.2 g, 0.145 mole in 150 ml), then with an aqueous sodium hydroxide solution (28 g, 0.07 mole in 56 ml) and subsequently dried over sodium sulfate. The dichloromethane solution was concentrated in vacuo and the residue was crystallized from dichloromethane petroleum ether bp 30°-60° C to give 11.16 g (mp 139°-141° C, 77.5% yield) of the title compound. mechanically stirred until a homogeneous solution was obtained it was stirred with a magnetic stirrer at room temperature in a tightly closed flask for one hour The solution was concentrated in vacuo for one hour the oily residue obtained the yellow solution was concentrated in vacuo the residue was dissolved in 200 ml of dichloromethane The dichloromethane solution was concentrated in vacuo the residue was crystallized from dichloromethane petroleum ether bp 30°-60° C

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

実験手順: 30.8 g (0.1 mol) of 1,2-diphenyl-3,5-dioxo-4-butyl-pyrazolidine are introduced with agitation into a 500 cc flask and mixed with 150 ml of acetone until complete dissolution. 10.8 g (0.1 mol) of 2-amino-4-methylpyridine which have previously been dissolved in 100 cc of acetone are then added and the mixture is boiled for 30 minutes. It is filtered cold, and 39 g of a product having a melting point of 121°-2° C are crystallized out. are then added It is filtered cold are crystallized out

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

実験手順: 30.8 g (0.1 mol) of 1,2-diphenyl-3,5-dioxo-4-butyl-pyrazolidine are introduced with agitation into a 500 cc flask and mixed with 150 ml of acetone until complete dissolution. 10.8 g (0.1 mol) of 2-amino-4-methylpyridine which have previously been dissolved in 100 cc of acetone are then added and the mixture is boiled for 30 minutes. It is filtered cold, and 39 g of a product having a melting point of 121°-2° C are crystallized out. are then added It is filtered cold are crystallized out

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

実験手順: Then, p-Toluenesulfonyl chloride (0.95 g, 5.0 mmole) was allowed to react with a dimethylformamide (20 ml) suspension of the Thallium (I) salt of phenylbutazone. Within a few minutes the solvent became pink and a yellow solid, instead of the white Thallium (I) salt of phenylbutazone, was observed suspended in the pink solution. The suspension was stirred overnight in a tightly sealed flask, then it was diluted with 100 ml of ether and filtered. The filtrate was concentrated in vacuo to remove the ether and the dimethylformamide was evaporated under a stream of nitrogen. The residue from the evaporation was suspended in dichloromethane and filtered. Analysis of the filtrate by TLC showed that it contained only one major component. The dichloromethane was evaporated in vacuo and the residue was crystallized from ether to give 0.76 g (mp 112°-121° C., 33% yield) of yellow crystals which contained only one components by TLC analysis. Recrystallization of the yellow crystals gave analytically pure crystals, mp 125°-127° C. with spectral properties identical to the crystals, mp 112°-121° C. Within a few minutes the solvent became pink filtered The filtrate was concentrated in vacuo to remove the ether the dimethylformamide was evaporated under a stream of nitrogen The residue from the evaporation filtered The dichloromethane was evaporated in vacuo the residue was crystallized from ether