Methyl cyclopentylacetate

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: 0.1 g (0.43 mmol) of 5-amino-1-(2,3-dimethylphenyl)-1H-pyrazole-4-carboxamide (Example 16A) is dissolved under argon in 6 ml of absolute ethanol and 0.24 g (1.7 mmol) of methyl cyclopentylacetate and 0.17 g (4.34 mmol) of 60% sodium hydride (suspension in mineral oil) are added. The reaction mixture is heated to reflux overnight. Cooling to room temperature is followed by acidification with concentrated hydrochloric acid. The mixture of sodium chloride and the product precipitated thereby is filtered off and washed several times with water and diethyl ether. Drying under high vacuum results in 69 mg (49% of theory) of the product as colourless solid. The reaction mixture is heated to reflux overnight the product precipitated thereby is filtered off washed several times with water and diethyl ether Drying under high vacuum

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

実験手順: 0.1 g (0.43 mmol) of 5-amino-1-(2,6-dimethylphenyl)-1H-pyrazole-4-carboxamide (Example 15A) is dissolved under argon in 6 ml of absolute ethanol and 0.24 g (1.7 mmol) of methyl cyclopentylacetate and 0.17 g (4.34 mmol) of 60% sodium hydride (suspension in mineral oil) are added. The reaction mixture is heated to reflux overnight. Cooling to room temperature is followed by acidification with concentrated hydrochloric acid. The sodium chloride precipitated thereby is filtered off. The filtrate is concentrated in vacuo, and the remaining residue is purified by preparative HPLC(YMC Gel ODS-AQ S 5/15 μm; eluent A: water, eluent B: acetonitrile; gradient: 0 min 30% B, 5 min 30% B, 50 min 95% B). 74 mg (53% of theory) of the product are obtained as a colourless solid. The reaction mixture is heated to reflux overnight The sodium chloride precipitated thereby is filtered off The filtrate is concentrated in vacuo the remaining residue is purified by preparative HPLC(YMC Gel ODS-AQ S 5/15 μm 0 min 30% B, 5 min 30% B, 50 min 95% B 74 mg (53% of theory) of the product are obtained as a colourless solid

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice-cooled and stirred solution of cyclopentylacetic acid (7.9 g, 0.062 mol) in 30 ml of ether was added an excess solution of diazomethane in ether. After concentration, the residue was distilled under reduced pressure to give a colorless transparent liquid of methyl cyclopentylacetate (yielded amount 5.5g, 0.039 mol, yield 62.5%, b.p. 64°-65° C./15 mmHg). Then, a solution of n-butyl lithium in hexane (1.58N, 55.7 ml, 0.088 mol) was added dropwise to a stirred solution of dimethyl methylphosphonate (10.9 g, 0.088 mol) in 100 ml of anhydrous THF under argon atmosphere at -78° C. After 30 minutes, the above-mentioned methyl cyclopentylacetate (5.0 g, 0.035 mol) in 10 ml of anhydrous THF was further added dropwise, and the mixture was stirred in situ for 30 minutes. This reaction mixture was allowed to warm to 0° C., diluted with 5.3 ml of acetic acid and 20 ml of water, and concentrated. 30 ml of water was added to the residue. The mixture was extracted with ethyl acetate (50 ml×2), and the combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give a colorless transparent oil of dimethyl 3-cyclopentyl-2-oxo-propylphosphonate (7.8 g, 0.033 mol, yield 94.7%, b.p. 110°-112° C./0.13 mmHg), which was assigned the structure by the following data: concentrated 30 ml of water was added to the residue The mixture was extracted with ethyl acetate (50 ml×2) the combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1) dried over anhydrous sodium sulfate concentrated The residue was distilled under reduced pressure

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

実験手順: To an ice-cooled and stirred solution of cyclopentylacetic acid (7.9 g, 0.062 mol) in 30 ml of ether was added an excess solution of diazomethane in ether. After concentration, the residue was distilled under reduced pressure to give a colorless transparent liquid of methyl cyclopentylacetate (yielded amount 5.5g, 0.039 mol, yield 62.5%, b.p. 64°-65° C./15 mmHg). Then, a solution of n-butyl lithium in hexane (1.58N, 55.7 ml, 0.088 mol) was added dropwise to a stirred solution of dimethyl methylphosphonate (10.9 g, 0.088 mol) in 100 ml of anhydrous THF under argon atmosphere at -78° C. After 30 minutes, the above-mentioned methyl cyclopentylacetate (5.0 g, 0.035 mol) in 10 ml of anhydrous THF was further added dropwise, and the mixture was stirred in situ for 30 minutes. This reaction mixture was allowed to warm to 0° C., diluted with 5.3 ml of acetic acid and 20 ml of water, and concentrated. 30 ml of water was added to the residue. The mixture was extracted with ethyl acetate (50 ml×2), and the combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give a colorless transparent oil of dimethyl 3-cyclopentyl-2-oxo-propylphosphonate (7.8 g, 0.033 mol, yield 94.7%, b.p. 110°-112° C./0.13 mmHg), which was assigned the structure by the following data: After concentration the residue was distilled under reduced pressure

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (12.7 g, 0.125) was dissolved in 150 mls of dry THF and cooled to -70° C. under N2. n-Bulb (80 ml of 1.6M solution in hexane, 0.125 moles) was added and the solution stirred for 5 minutes at -70° C. Methyl cyclopentaneacetate (17 g, 0.125 mole) in 50 mls of THF was added at -70° C. over 15 minutes and the reaction was stirred at -70° C. for 15 more minutes. A solution of cyclohexanone (11.3 g, 0.115 moles) in THF (50ml) was then added at -70° C. over 1/2 hour and stirred in the cold for 1 hour. The reaction was warmed to room temperature over 1 hour and quenched with 5 mls of 1N HCl. The solvent was removed on the rotary evaporator and ethyl acetate added. The solution was then washed with saturated NaHCO3 and the layers were separated. The organic layer was dried over Na2SO4. The drying agent was filtered and the filtrate stripped to give a residue which was chromatographed on silica gel using 7% ethyl acetate/hexane to give 27.8 g (92% yield) of the title compound. the reaction was stirred at -70° C. for 15 more minutes stirred in the cold for 1 hour The reaction was warmed to room temperature over 1 hour quenched with 5 mls of 1N HCl The solvent was removed on the rotary evaporator and ethyl acetate added The solution was then washed with saturated NaHCO3 the layers were separated The organic layer was dried over Na2SO4 The drying agent was filtered to give a residue which was chromatographed on silica gel using 7% ethyl acetate/hexane

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (12.7 g, 0.125) was dissolved in 150 mls of dry THF and cooled to -70° C. under N2. n-Bulb (80 ml of 1.6M solution in hexane, 0.125 moles) was added and the solution stirred for 5 minutes at -70° C. Methyl cyclopentaneacetate (17 g, 0.125 mole) in 50 mls of THF was added at -70° C. over 15 minutes and the reaction was stirred at -70° C. for 15 more minutes. A solution of cyclohexanone (11.3 g, 0.115 moles) in THF (50ml) was then added at -70° C. over 1/2 hour and stirred in the cold for 1 hour. The reaction was warmed to room temperature over 1 hour and quenched with 5 mls of 1N HCl. The solvent was removed on the rotary evaporator and ethyl acetate added. The solution was then washed with saturated NaHCO3 and the layers were separated. The organic layer was dried over Na2SO4. The drying agent was filtered and the filtrate stripped to give a residue which was chromatographed on silica gel using 7% ethyl acetate/hexane to give 27.8 g (92% yield) of the title compound. the reaction was stirred at -70° C. for 15 more minutes stirred in the cold for 1 hour The reaction was warmed to room temperature over 1 hour quenched with 5 mls of 1N HCl The solvent was removed on the rotary evaporator and ethyl acetate added The solution was then washed with saturated NaHCO3 the layers were separated The organic layer was dried over Na2SO4 The drying agent was filtered to give a residue which was chromatographed on silica gel using 7% ethyl acetate/hexane

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

実験手順: 0.1 g (0.43 mmol) of 5-amino-1-(2,3-dimethylphenyl)-1H-pyrazole-4-carboxamide (Example 16A) is dissolved under argon in 6 ml of absolute ethanol and 0.24 g (1.7 mmol) of methyl cyclopentylacetate and 0.17 g (4.34 mmol) of 60% sodium hydride (suspension in mineral oil) are added. The reaction mixture is heated to reflux overnight. Cooling to room temperature is followed by acidification with concentrated hydrochloric acid. The mixture of sodium chloride and the product precipitated thereby is filtered off and washed several times with water and diethyl ether. Drying under high vacuum results in 69 mg (49% of theory) of the product as colourless solid. The reaction mixture is heated to reflux overnight the product precipitated thereby is filtered off washed several times with water and diethyl ether Drying under high vacuum

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

実験手順: 0.1 g (0.43 mmol) of 5-amino-1-(2,6-dimethylphenyl)-1H-pyrazole-4-carboxamide (Example 15A) is dissolved under argon in 6 ml of absolute ethanol and 0.24 g (1.7 mmol) of methyl cyclopentylacetate and 0.17 g (4.34 mmol) of 60% sodium hydride (suspension in mineral oil) are added. The reaction mixture is heated to reflux overnight. Cooling to room temperature is followed by acidification with concentrated hydrochloric acid. The sodium chloride precipitated thereby is filtered off. The filtrate is concentrated in vacuo, and the remaining residue is purified by preparative HPLC(YMC Gel ODS-AQ S 5/15 μm; eluent A: water, eluent B: acetonitrile; gradient: 0 min 30% B, 5 min 30% B, 50 min 95% B). 74 mg (53% of theory) of the product are obtained as a colourless solid. The reaction mixture is heated to reflux overnight The sodium chloride precipitated thereby is filtered off The filtrate is concentrated in vacuo the remaining residue is purified by preparative HPLC(YMC Gel ODS-AQ S 5/15 μm 0 min 30% B, 5 min 30% B, 50 min 95% B 74 mg (53% of theory) of the product are obtained as a colourless solid

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: 0.1 g (0.43 mmol) of 5-amino-1-(2,3-dimethylphenyl)-1H-pyrazole-4-carboxamide (Example 16A) is dissolved under argon in 6 ml of absolute ethanol and 0.24 g (1.7 mmol) of methyl cyclopentylacetate and 0.17 g (4.34 mmol) of 60% sodium hydride (suspension in mineral oil) are added. The reaction mixture is heated to reflux overnight. Cooling to room temperature is followed by acidification with concentrated hydrochloric acid. The mixture of sodium chloride and the product precipitated thereby is filtered off and washed several times with water and diethyl ether. Drying under high vacuum results in 69 mg (49% of theory) of the product as colourless solid. The reaction mixture is heated to reflux overnight the product precipitated thereby is filtered off washed several times with water and diethyl ether Drying under high vacuum

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

実験手順: 0.1 g (0.43 mmol) of 5-amino-1-(2,6-dimethylphenyl)-1H-pyrazole-4-carboxamide (Example 15A) is dissolved under argon in 6 ml of absolute ethanol and 0.24 g (1.7 mmol) of methyl cyclopentylacetate and 0.17 g (4.34 mmol) of 60% sodium hydride (suspension in mineral oil) are added. The reaction mixture is heated to reflux overnight. Cooling to room temperature is followed by acidification with concentrated hydrochloric acid. The sodium chloride precipitated thereby is filtered off. The filtrate is concentrated in vacuo, and the remaining residue is purified by preparative HPLC (YMC Gel ODS-AQ S 5/15 μm; eluent A: water, eluent B: acetonitrile; gradient: 0 min 30% B, 5 min 30% B, 50 min 95% B). 74 mg (53% of theory) of the product are obtained as a colourless solid. The reaction mixture is heated to reflux overnight The sodium chloride precipitated thereby is filtered off The filtrate is concentrated in vacuo the remaining residue is purified by preparative HPLC (YMC Gel ODS-AQ S 5/15 μm; eluent A: water, eluent B: acetonitrile; gradient: 0 min 30% B, 5 min 30% B, 50 min 95% B) 74 mg (53% of theory) of the product are obtained as a colourless solid