3-PYRAZOLIDINONE HYDROCHLORIDE

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

実験手順: As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using 3-pyrazolidinone hydrochloride instead of 2-aminoethyl isopropylether, to the title compound (12 mg, 5%) which was obtained as a white solid. MS: m/e=375.0 [M−H]−.

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

実験手順: As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using 3-pyrazolidinone hydrochloride instead of 2-aminoethyl isopropylether, to the title compound (12 mg, 5%) which was obtained as a white solid. MS: m/e=375.0 [M−H]−.

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

実験手順: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (42 mg. 0.125 mmol), 3-pyrazolidinone hydrochloride (23 mg, 0.188 mmol) and sodium triacetoxyborohydride (40 mg, 0.188 mmol) to afford 8 mg (16%) of the desired product after purification. Prepared

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

実験手順: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (42 mg. 0.125 mmol), 3-pyrazolidinone hydrochloride (23 mg, 0.188 mmol) and sodium triacetoxyborohydride (40 mg, 0.188 mmol) to afford 8 mg (16%) of the desired product after purification. Prepared

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

実験手順: To a suspension of pyrazolidin-3-one hydrogen chloride (5.00 g, 40.8 mmol) in DCM (120 mL) at 0° C. was added DIEA (2.5 eq), followed by CbzCl (1.15 eq). The resulting clear solution was warmed to it and stirred 3 h. The reaction mixture was washed with brine. The aqueous layer was separated and back-extracted with DCM (×2). The combined organic layers were dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-100% EtOAc/Hexanes, Rf=0.35 in 100% EtOAc) to afford the desired product as a white solid (5.31 g). The resulting clear solution was warmed to it The reaction mixture was washed with brine The aqueous layer was separated back-extracted with DCM (×2) The combined organic layers were dried over Na2SO4 concentrated The crude product was purified by a SiO2 column (0-100% EtOAc/Hexanes, Rf=0.35 in 100% EtOAc)

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

実験手順: To a suspension of pyrazolidin-3-one hydrogen chloride (5.00 g, 40.8 mmol) in DCM (120 mL) at 0° C. was added DIEA (2.5 eq), followed by CbzCl (1.15 eq). The resulting clear solution was warmed to it and stirred 3 h. The reaction mixture was washed with brine. The aqueous layer was separated and back-extracted with DCM (×2). The combined organic layers were dried over Na2SO4, and concentrated. The crude product was purified by a SiO2 column (0-100% EtOAc/Hexanes, Rf=0.35 in 100% EtOAc) to afford the desired product as a white solid (5.31 g). The resulting clear solution was warmed to it The reaction mixture was washed with brine The aqueous layer was separated back-extracted with DCM (×2) The combined organic layers were dried over Na2SO4 concentrated The crude product was purified by a SiO2 column (0-100% EtOAc/Hexanes, Rf=0.35 in 100% EtOAc)

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

実験手順: 1.00 g (5.29 mmol) 4-fluoro-3-trifluoromethyl-benzonitrile are stirred together with 1.35 g (12.0 mmol) potassium-tert.-butoxide in 4 ml DMSO at ambient temperature under an argon atmosphere for 35 min and then 1.00 g (8.16 mmol) pyrazolidin-3-on-hydrochloride in 3 ml DMSO are added. After stirring at ambient temperature for 68 h the reaction mixture is poured into semisat. sodium chloride solution and extracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate and evaporated down completely i. vac. is poured into semisat sodium chloride solution and extracted with ethyl acetate The combined organic phases are dried over magnesium sulphate evaporated down completely

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

実験手順: Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (42 mg. 0.125 mmol), 3-pyrazolidinone hydrochloride (23 mg, 0.188 mmol) and sodium triacetoxyborohydride (40 mg, 0.188 mmol) to afford 8 mg (16%) of the desired product after purification. Prepared

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

実験手順: A mixture of 10-(4-acetonylphenoxy)decylbromide, ethylene ketal (3.0 g), potassium carbonate (3.8 g), pyrazolidin-3-one hydrochloride (1.47 g) and potassium iodide (0.5 g) in acetonitrile:water (95:5), was heated under reflux for 3 hr. The reaction mixture was allowed to cool, filtered and the solvent evaporated in vacuo. The residue was dissolved in chloroform, washed with water (2×50 ml), dried (magnesium sulphate), fitered and the solvent removed in vacuo. The residue was dissolved in acetone (50 ml) and treated with 2M hydrochloric acid solution (3 ml) and allowed to stand at room temperature for 3 hr. The solvent was removed in vacuo and the residue was dissolved in chloroform and washed with 1.2M sodium bicarbonate solution (1×50 ml), water (2×50 ml), dried (magnesium sulphate), filtered and the solvent removed in vacuo to give 1-[10-(4-acetonylphenoxy)decyl]pyrazolidin-3-one (0.66 g). was heated under reflux for 3 hr to cool filtered the solvent evaporated in vacuo The residue was dissolved in chloroform washed with water (2×50 ml) dried (magnesium sulphate) the solvent removed in vacuo The residue was dissolved in acetone (50 ml) treated with 2M hydrochloric acid solution (3 ml) The solvent was removed in vacuo the residue was dissolved in chloroform washed with 1.2M sodium bicarbonate solution (1×50 ml), water (2×50 ml) dried (magnesium sulphate) filtered the solvent removed in vacuo

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

実験手順: A mixture of 10-(4-acetonylphenoxy)decylbromide, ethylene ketal (3.0 g), potassium carbonate (3.8 g), pyrazolidin-3-one hydrochloride (1.47 g) and potassium iodide (0.5 g) in acetonitrile:water (95:5), was heated under reflux for 3 hr. The reaction mixture was allowed to cool, filtered and the solvent evaporated in vacuo. The residue was dissolved in chloroform, washed with water (2×50 ml), dried (magnesium sulphate), fitered and the solvent removed in vacuo. The residue was dissolved in acetone (50 ml) and treated with 2M hydrochloric acid solution (3 ml) and allowed to stand at room temperature for 3 hr. The solvent was removed in vacuo and the residue was dissolved in chloroform and washed with 1.2M sodium bicarbonate solution (1×50 ml), water (2×50 ml), dried (magnesium sulphate), filtered and the solvent removed in vacuo to give 1-[10-(4-acetonylphenoxy)decyl]pyrazolidin-3-one (0.66 g). was heated under reflux for 3 hr to cool filtered the solvent evaporated in vacuo The residue was dissolved in chloroform washed with water (2×50 ml) dried (magnesium sulphate) the solvent removed in vacuo The residue was dissolved in acetone (50 ml) treated with 2M hydrochloric acid solution (3 ml) The solvent was removed in vacuo the residue was dissolved in chloroform washed with 1.2M sodium bicarbonate solution (1×50 ml), water (2×50 ml) dried (magnesium sulphate) filtered the solvent removed in vacuo

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

実験手順: As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using 3-pyrazolidinone hydrochloride instead of 2-aminoethyl isopropylether, to the title compound (12 mg, 5%) which was obtained as a white solid. MS: m/e=375.0 [M−H]−.

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

実験手順: As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using 3-pyrazolidinone hydrochloride instead of 2-aminoethyl isopropylether, to the title compound (12 mg, 5%) which was obtained as a white solid. MS: m/e=375.0 [M−H]−.