2-[2-(2-bromoethoxy)ethyl]isoindole-1,3-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: 1.73 g. (6 mmol) Methanediphosphonic acid tetraethyl ester is added dropwise to 144 mg. (6 mmol) sodium hydride in 5 ml. anhydrous toluene. After completion of the evolution of hydrogen, stirring is continued for 30 minutes and then 1.7 g. (6 mmol) N-(2-bromoethoxyethyl)-phthalimide (m.p. 83°-85° C.) is added dropwise thereto. The reaction mixture is stirred for 24 hours at ambient temperature, then mixed with water, the aqueous phase is adjusted to pH 5 with 2N hydrochloric acid and the organic phase is separated off, dried and evaporated. The residue is purified over 250 g. silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g. (12% of theory) 5-phthalimido-3-oxapentane-1,1-diphosphonic acid tetraethyl ester in the form of an oily substance. The ester is subsequently boiled under reflux for 12 hours with 10 ml. 6N hydrochloric acid and, after cooling, the precipitated phthalic acid is filtered off with suction. The residue is taken up in water, the solution is adjusted with 2N aqueous sodium hydroxide solution to pH 5 and mixed, while cooling with ice, with a large excess of methanol. The precipitate obtained is filtered off with suction and dried. There is obtained 0.125 g. (7.2% of theory) of the desired compound in the form of the monosodium salt containing 1 mole water of crystallisation; m.p.>300° C.; Mrel =0.30. the organic phase is separated off dried evaporated The residue is purified over 250 g silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g under reflux for 12 hours with 10 ml the precipitated phthalic acid is filtered off with suction mixed while cooling with ice The precipitate obtained is filtered off with suction dried There is obtained 0.125 g

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

実験手順: To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (3.00 g, 20 mmoles) and N-[2-[2-(bromo)ethyloxy]ethyl]phthalimide (5.96 g, 20 mmoles) in ethanol (200 ml) was added triethylamine (4.2 ml, 30 mmoles) and the mixture was stirred at room temperature for 12 hours and heated at reflux for 3 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled off. Then, the residue was purified by column chromatography (eluent:ethyl acetate) to obtain 4.00 g of the desired product (54.5%, light tan solid). heated at reflux for 3 hours After the solvent was distilled off chloroform was added to the residue, which was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off Then, the residue was purified by column chromatography (eluent:ethyl acetate)

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

実験手順: 1.73 g. (6 mmol) Methanediphosphonic acid tetraethyl ester is added dropwise to 144 mg. (6 mmol) sodium hydride in 5 ml. anhydrous toluene. After completion of the evolution of hydrogen, stirring is continued for 30 minutes and then 1.7 g. (6 mmol) N-(2-bromoethoxyethyl)-phthalimide (m.p. 83°-85° C.) is added dropwise thereto. The reaction mixture is stirred for 24 hours at ambient temperature, then mixed with water, the aqueous phase is adjusted to pH 5 with 2N hydrochloric acid and the organic phase is separated off, dried and evaporated. The residue is purified over 250 g. silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g. (12% of theory) 5-phthalimido-3-oxapentane-1,1-diphosphonic acid tetraethyl ester in the form of an oily substance. The ester is subsequently boiled under reflux for 12 hours with 10 ml. 6N hydrochloric acid and, after cooling, the precipitated phthalic acid is filtered off with suction. The residue is taken up in water, the solution is adjusted with 2N aqueous sodium hydroxide solution to pH 5 and mixed, while cooling with ice, with a large excess of methanol. The precipitate obtained is filtered off with suction and dried. There is obtained 0.125 g. (7.2% of theory) of the desired compound in the form of the monosodium salt containing 1 mole water of crystallisation; m.p.>300° C.; Mrel =0.30. the organic phase is separated off dried evaporated The residue is purified over 250 g silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g under reflux for 12 hours with 10 ml the precipitated phthalic acid is filtered off with suction mixed while cooling with ice The precipitate obtained is filtered off with suction dried There is obtained 0.125 g

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

実験手順: To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (3.00g, 20 mmoles) and N-[2-[2-(bromo)ethyloxy]ethyl]phthalimide (5.96 g, 20 mmoles) in ethanol (200 ml) was added triethylamine (4.2 ml, 30 mmoles) and the mixture was stirred at room temperature for 12 hours and heated at reflux for 3 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled off. Then, the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 4.00 g of the desired product (54.5%, light tan solid). heated at reflux for 3 hours After the solvent was distilled off chloroform was added to the residue, which was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off Then, the residue was purified by column chromatography (eluent: ethyl acetate)

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

実験手順: To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (3.00g, 20 mmoles) and N-[2-[2-(bromo)ethyloxy]ethyl]phthalimide (5.96 g, 20 mmoles) in ethanol (200 ml) was added triethylamine (4.2 ml, 30 mmoles) and the mixture was stirred at room temperature for 12 hours and heated at reflux for 3 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled off. Then, the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 4.00 g of the desired product (54.5%, light tan solid). heated at reflux for 3 hours After the solvent was distilled off chloroform was added to the residue, which was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off Then, the residue was purified by column chromatography (eluent: ethyl acetate)

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

実験手順: To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (3.00 g, 20 mmoles) and N-[2-[2-(bromo)ethyloxy]ethyl]phthalimide (5.96 g, 20 mmoles) in ethanol (200 ml) was added triethylamine (4.2 ml, 30 mmoles) and the mixture was stirred at room temperature for 12 hours and heated at reflux for 3 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled off. Then, the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 4.00 g of the desired product (54.5%, light tan solid). heated at reflux for 3 hours After the solvent was distilled off chloroform was added to the residue, which was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off Then, the residue was purified by column chromatography (eluent: ethyl acetate)

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

実験手順: To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (3.00 g, 20 mmoles) and N-[2-[2-(bromo)ethyloxy]ethyl]phthalimide (5.96 g, 20 mmoles) in ethanol (200 ml) was added triethylamine (4.2 ml, 30 mmoles) and the mixture was stirred at room temperature for 12 hours and heated at reflux for 3 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled off. Then, the residue was purified by column chromatography (eluent:ethyl acetate) to obtain 4.00 g of the desired product (54.5%, light tan solid). heated at reflux for 3 hours After the solvent was distilled off chloroform was added to the residue, which was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off Then, the residue was purified by column chromatography (eluent:ethyl acetate)

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

実験手順: 1.73 g. (6 mmol) Methanediphosphonic acid tetraethyl ester is added dropwise to 144 mg. (6 mmol) sodium hydride in 5 ml. anhydrous toluene. After completion of the evolution of hydrogen, stirring is continued for 30 minutes and then 1.7 g. (6 mmol) N-(2-bromoethoxyethyl)-phthalimide (m.p. 83°-85° C.) is added dropwise thereto. The reaction mixture is stirred for 24 hours at ambient temperature, then mixed with water, the aqueous phase is adjusted to pH 5 with 2N hydrochloric acid and the organic phase is separated off, dried and evaporated. The residue is purified over 250 g. silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g. (12% of theory) 5-phthalimido-3-oxapentane-1,1-diphosphonic acid tetraethyl ester in the form of an oily substance. The ester is subsequently boiled under reflux for 12 hours with 10 ml. 6N hydrochloric acid and, after cooling, the precipitated phthalic acid is filtered off with suction. The residue is taken up in water, the solution is adjusted with 2N aqueous sodium hydroxide solution to pH 5 and mixed, while cooling with ice, with a large excess of methanol. The precipitate obtained is filtered off with suction and dried. There is obtained 0.125 g. (7.2% of theory) of the desired compound in the form of the monosodium salt containing 1 mole water of crystallisation; m.p.>300° C.; Mrel =0.30. the organic phase is separated off dried evaporated The residue is purified over 250 g silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g under reflux for 12 hours with 10 ml the precipitated phthalic acid is filtered off with suction mixed while cooling with ice The precipitate obtained is filtered off with suction dried There is obtained 0.125 g

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

実験手順: To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (3.00g, 20 mmoles) and N-[2-[2-(bromo)ethyloxy]ethyl]phthalimide (5.96 g, 20 mmoles) in ethanol (200 ml) was added triethylamine (4.2 ml, 30 mmoles) and the mixture was stirred at room temperature for 12 hours and heated at reflux for 3 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water, dried over anhydrous magnesium sulfate and the solvent was distilled off. Then, the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 4.00 g of the desired product (54.5%, light tan solid). heated at reflux for 3 hours After the solvent was distilled off chloroform was added to the residue, which was washed with water dried over anhydrous magnesium sulfate the solvent was distilled off Then, the residue was purified by column chromatography (eluent: ethyl acetate)