methyl 8-chloro-8-oxooctanoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: To a solution of 3-amino-biphenyl (315, 536 mg, 3.17 mmol) in THF/pyridine (2:1, 6 mL) was added methyl 7-(chlorocarbonyl)heptanoate (0.49 mL, 3.48 mmol), and the resulting solution was stirred at room temperature for 16 h. After dilution with saturated NaCl solution (15 mL) and extraction with ethyl acetate, the organic layer was dried over Na2SO4, filtered and concentrated. The residue was then dissolved in THF/methanol/H2O (1:1:2, 8 mL), followed by the treatment of LiOH—H2O (665 mg, 15.85 mmol). The reaction mixture was stirred at room temperature for 1 h prior to acidification (pH=1), and extraction with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated. After purification by flash chromatography (eluent 0-100% EtOAc in hexanes), the title compound 316 was obtained as a white solid (889 mg, 86% yield). 1H NMR: (DMSO) δ (ppm): 1.30-1.40 (m, 4H), 1.50-1.59 (m, 2H), 1.60-1.68 (m, 2H), 2.24 (t, J=7.4 Hz, 2H), 2.37 (t, J=7.4 Hz, 2H), 7.32 (dt, J=7.8, 1.6 Hz, 1H), 7.36-7.42 (m, 2H), 7.46-7.52 (m, 2H), 7.58-7.64 (m, 3H), 7.96 (s, 1H), 10.07 (br s, 1H). MS: (calc.) 325.4; (obt.) 326.1 (MH)+. After dilution with saturated NaCl solution (15 mL) and extraction with ethyl acetate the organic layer was dried over Na2SO4 filtered concentrated The residue was then dissolved in THF/methanol/H2O (1:1:2, 8 mL) The reaction mixture was stirred at room temperature for 1 h to acidification (pH=1), and extraction with ethyl acetate The organic layer was dried over Na2SO4 filtered concentrated After purification by flash chromatography (eluent 0-100% EtOAc in hexanes)

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

実験手順: To a solution of 3-amino-biphenyl (315, 536 mg, 3.17 mmol) in THF/pyridine (2:1, 6 mL) was added methyl 7-(chlorocarbonyl)heptanoate (0.49 mL, 3.48 mmol), and the resulting solution was stirred at room temperature for 16 h. After dilution with saturated NaCl solution (15 mL) and extraction with ethyl acetate, the organic layer was dried over Na2SO4, filtered and concentrated. The residue was then dissolved in THF/methanol/H2O (1:1:2, 8 mL), followed by the treatment of LiOH—H2O (665 mg, 15.85 mmol). The reaction mixture was stirred at room temperature for 1 h prior to acidification (pH=1), and extraction with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated. After purification by flash chromatography (eluent 0-100% EtOAc in hexanes), the title compound 316 was obtained as a white solid (889 mg, 86% yield). 1H NMR: (DMSO) δ (ppm): 1.30-1.40 (m, 4H), 1.50-1.59 (m, 2H), 1.60-1.68 (m, 2H), 2.24 (t, J=7.4 Hz, 2H), 2.37 (t, J=7.4 Hz, 2H), 7.32 (dt, J=7.8, 1.6 Hz, 1H), 7.36-7.42 (m, 2H), 7.46-7.52 (m, 2H), 7.58-7.64 (m, 3H), 7.96 (s, 1H), 10.07 (br s, 1H). MS: (calc.) 325.4; (obt.) 326.1 (MH)+. After dilution with saturated NaCl solution (15 mL) and extraction with ethyl acetate the organic layer was dried over Na2SO4 filtered concentrated The residue was then dissolved in THF/methanol/H2O (1:1:2, 8 mL) The reaction mixture was stirred at room temperature for 1 h to acidification (pH=1), and extraction with ethyl acetate The organic layer was dried over Na2SO4 filtered concentrated After purification by flash chromatography (eluent 0-100% EtOAc in hexanes)

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

実験手順: 600 mg (1.36 mmol) of 5-(3′-methylaminomethylbiphenyl-4-ylmethyl)thiazolidine-2,4-dione, 10 ml of THF and 600 μl (4.3 mmol) of triethylamine are introduced into a round-bottomed flask and under a nitrogen stream. 220 μl (1.55 mmol) of methyl 8-chloro-8-oxooctanoate are added dropwise and the mixture is stirred for one hour. The reaction medium is poured into water, extracted with dichloromethane, the organic phase decanted off, washed with water, dried over magnesium sulphate and evaporated off. The residue obtained is purified by chromatography on a silica column eluted with a dichloromethane and ethyl acetate (80-20) mixture. After evaporation of the solvents, 350 mg (50%) of methyl 7-{[4′-(2,4-dioxothiazolidin-5-ylmethyl)biphenyl-3-ylmethyl]methylcarbamoyl}heptanoate are recovered in the form of an oil. extracted with dichloromethane the organic phase decanted off washed with water dried over magnesium sulphate evaporated off The residue obtained is purified by chromatography on a silica column eluted with a dichloromethane and ethyl acetate (80-20) mixture After evaporation of the solvents, 350 mg (50%) of methyl 7-{[4′-(2,4-dioxothiazolidin-5-ylmethyl)biphenyl-3-ylmethyl]methylcarbamoyl}heptanoate are recovered in the form of an oil

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

実験手順: Aluminium chloride (2.58 g) was added to a mixture of methyl 8-chloro-8-oxooctanoate (2.00 g) and anisole (5 ml) at 0° C. After stirring at room temperature for 14 hours, the reaction mixture was poured onto ice (50 g), stirred at room temperature for 1 hour and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain methyl 8-(4-methoxyphenyl)-8-oxooctanoate (2.37 g, yield 88%) as crystals. The crystals were recrystallized from ethyl acetate-hexane to obtain colorless crystals. m.p. 57-58° C. the reaction mixture was poured onto ice (50 g) stirred at room temperature for 1 hour extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated

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

実験手順: To a solution of N1-cyclopropylbenzene-1,2-diamine (221 mg, 1.49 mmol) and triethylamine (0.3 mL, 2.2 mmol) in DMF was added a solution of methyl 8-chloro-8-oxooctanoate (260 mg, 1.3 mmol) in DMF at 0° C. drop-wise. The reaction was stirred overnight at room temperature, diluted with ethyl acetate and washed with 1 N HCl, saturated sodium bicarbonate solution and brine. The separated organic layer was concentrated to give crude methyl 8-(2-(cyclopropylamino)phenylamino)-8-oxooctanoate (390 mg) washed with 1 N HCl, saturated sodium bicarbonate solution and brine The separated organic layer was concentrated

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

実験手順: To a solution of methyl 8-chloro-8-oxooctanoate (200 mg, 0.97 mmol) in DMF at 0° C. was added a solution of 4-nitrobiphenyl-3-amine (207 mg, 0.97 mmol) and triethylamine (0.46 mL, 3.3 mmol) in DMF drop-wise. The reaction was stirred overnight at room temperature, diluted with ethyl acetate and washed with 1 N HCl, saturated sodium bicarbonate solution and brine. The separated organic layer was concentrated and purified by biotage column chromatography to give methyl 8-(4-nitrobiphenyl-3-ylamino)-8-oxooctanoate (279 mg) washed with 1 N HCl, saturated sodium bicarbonate solution and brine The separated organic layer was concentrated purified by biotage column chromatography