3603-45-0

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: Diethyl azodicarboxylate (378 μl, 2.4 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (292 mg, 0.8 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (629 mg, 2.4 mmol) and 2-(2-morpholinoethoxy)ethanol (196 mg, 1.12 mmol), (prepared as described for the starting material in Example 53), in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours at ambient temperature and the mixture was purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol 6/3/1). The purified product was dissolved in methylene chloride/methanol and the insolubles were removed by filtration. 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (232 mg, 49%). (prepared (prepared the mixture was purified by pouring it directly on to a column of silica eluting with methylene chloride/acetonitrile/methanol 6/3/1) The purified product was dissolved in methylene chloride/methanol the insolubles were removed by filtration 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate the volatiles were removed by evaporation The residue was triturated with ether collected by filtration washed with ether dried under vacuum

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

実験手順: Diethyl azodicarboxylate (378 μl, 2.4 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (292 mg, 0.8 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (629 mg, 2.4 mmol) and 2-(2-morpholinoethoxy)ethanol (196 mg, 1.12 mmol), (prepared as described for the starting material in Example 53), in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours at ambient temperature and the mixture was purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol 6/3/1). The purified product was dissolved in methylene chloride/methanol and the insolubles were removed by filtration. 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (232 mg, 49%). (prepared (prepared the mixture was purified by pouring it directly on to a column of silica eluting with methylene chloride/acetonitrile/methanol 6/3/1) The purified product was dissolved in methylene chloride/methanol the insolubles were removed by filtration 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate the volatiles were removed by evaporation The residue was triturated with ether collected by filtration washed with ether dried under vacuum

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

実験手順: 2-(2-Chloroethoxy)ethanol (1.25 g, 10 mmol) was added to a mixture of morpholine (2.58 g, 30 mmol) and potassium carbonate (5.5 g, 40 mmol) in acetonitrile (50 ml). The mixture was heated at reflux for 6 hours and then stirred for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10 and then 80/20) to give 2-(2-morpholinoethoxy)ethanol (600 mg, 34%). The mixture was heated at reflux for 6 hours The insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5

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

実験手順: Diethyl azodicarboxylate (209 mg, 1.2 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6 methoxyquinazoline (128 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), triphenylphosphine (314 mg, 1.2 mmol) and 2-(2-morpholinoethoxy)ethanol (97 mg, 0.56 mmol) in methylene chloride (4 ml) under nitrogen. The mixture was stirs for 1 hour at ambient temperature, triphenylphosphine (105 mg, 0.4 mmol), 2-(2-morpholinoethoxy)ethanol (49 mg, 0.28 mmol) and diethyl azodicarboxylate (70 mg, 0.4 mmol) were added. The mixture was stirred for 1 hour at ambient temperature and was purified by pouring directly onto a silica column eluting with methylene chloride/acetonitrile/methanol (6/3/1). The purified product was triturated with ether, collected by filtration and dissolved in methylene chloride. 2M Ethereal hydrogen chloride (0.5 ml) was added and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (100 mg, 45%). (prepared for 1 hour at ambient temperature was purified by pouring directly onto a silica column eluting with methylene chloride/acetonitrile/methanol (6/3/1) The purified product was triturated with ether collected by filtration dissolved in methylene chloride 2M Ethereal hydrogen chloride (0.5 ml) was added the resulting precipitate was collected by filtration washed with ether dried under vacuum

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

実験手順: Diethyl azodicarboxylate (209 mg, 1.2 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6 methoxyquinazoline (128 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), triphenylphosphine (314 mg, 1.2 mmol) and 2-(2-morpholinoethoxy)ethanol (97 mg, 0.56 mmol) in methylene chloride (4 ml) under nitrogen. The mixture was stirs for 1 hour at ambient temperature, triphenylphosphine (105 mg, 0.4 mmol), 2-(2-morpholinoethoxy)ethanol (49 mg, 0.28 mmol) and diethyl azodicarboxylate (70 mg, 0.4 mmol) were added. The mixture was stirred for 1 hour at ambient temperature and was purified by pouring directly onto a silica column eluting with methylene chloride/acetonitrile/methanol (6/3/1). The purified product was triturated with ether, collected by filtration and dissolved in methylene chloride. 2M Ethereal hydrogen chloride (0.5 ml) was added and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (100 mg, 45%). (prepared for 1 hour at ambient temperature was purified by pouring directly onto a silica column eluting with methylene chloride/acetonitrile/methanol (6/3/1) The purified product was triturated with ether collected by filtration dissolved in methylene chloride 2M Ethereal hydrogen chloride (0.5 ml) was added the resulting precipitate was collected by filtration washed with ether dried under vacuum

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

実験手順: 2-(2-Chloroethoxy)ethanol (1.25 g, 10 mmol) was added to a mixture of morpholine (2.58 g, 30 mmol) and potassium carbonate (5.5 g, 40 mmol) in acetonitrile (50 ml). The mixture was heated at reflux for 6 hours and then stirred for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10 and then 80/20) to give 2-(2-morpholinoethoxy)ethanol (600 mg, 34%). The mixture was heated at reflux for 6 hours The insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5

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

実験手順: 2-(2-Chloroethoxy)ethanol (1.25 g, 10 mmol) was added to a mixture of morpholine (2.58 g, 30 mmol) and potassium carbonate (5.5 g, 40 mmol) in acetonitrile (50 ml). The mixture was heated at reflux for 6 hours and then stirred for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10 and then 80/20) to give 2-(2-morpholinoethoxy)ethanol (600 mg, 34%). The mixture was heated at reflux for 6 hours The insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5

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

実験手順: 2-(2-Chloroethoxy)ethanol (1.25 g, 10 mmol) was added to a mixture of morpholine (2.58 g, 30 mmol) and potassium carbonate (5.5 g, 40 mmol) in acetonitrile (50 ml). The mixture was heated at reflux for 6 hours and then stirred for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10 and then 80/20) to give 2-(2-morpholinoethoxy)ethanol (600 mg, 34%). The mixture was heated at reflux for 6 hours The insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5

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

実験手順: 2-(2-Chloroethoxy)ethanol (1.25 g, 10 mmol) was added to a mixture of morpholine (2.58 g, 30 mmol) and potassium carbonate (5.5 g, 40 mmol) in acetonitrile (50 ml). The mixture was heated at reflux for 6 hours and then stirred for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10 and then 80/20) to give 2-(2-morpholinoethoxy)ethanol (600 mg, 34%). The mixture was heated at reflux for 6 hours The insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5

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: Diethyl azodicarboxylate (378 μl, 2.4 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (292 mg, 0.8 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (629 mg, 2.4 mmol) and 2-(2-morpholinoethoxy)ethanol (196 mg, 1.12 mmol), (prepared as described for the starting material in Example 53), in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 3.5 hours at ambient temperature and the mixture was purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol 6/3/1). The purified product was dissolved in methylene chloride/methanol and the insolubles were removed by filtration. 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (232 mg, 49%). (prepared (prepared the mixture was purified by pouring it directly on to a column of silica eluting with methylene chloride/acetonitrile/methanol 6/3/1) The purified product was dissolved in methylene chloride/methanol the insolubles were removed by filtration 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate the volatiles were removed by evaporation The residue was triturated with ether collected by filtration washed with ether dried under vacuum