3-(叔丁氧羰基)噻唑烷-4-羧酸

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-tert-butoxycarbonylthiazolidine4-carboxylic acid (2.3 g, 10.0 mmol) in THF (30 ml) was added BH3.THF(1.0 M solution in THF, 20.0 ml, 20.0 mmol) at 0° C. After stirred at room temperature for 1.0 h, the reaction mixture was heated under reflux for 1.0 hr. After cooled, the mixture was concentrated in vacuo. Water was added thereto at 0° C., and extracted with EtOAc. The extract was washed with water, then dried over Na2SO4, and concentrated in vacuo to give 3-tert-butoxycarbonyl-5-hydroxymethylthiazolidine (2.0 g , quant) as a a colorless oil. 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.80–2.85 (m, 1H), 3.13–3.17 (m, 1H), 3.20–3.30 (m, 1H), 3.64–3.70 (m, 2H), 4.34 (br s, 1H), 4.60 (br s, 1H). the reaction mixture was heated under reflux for 1.0 hr After cooled the mixture was concentrated in vacuo Water was added at 0° C., and extracted with EtOAc The extract was washed with water dried over Na2SO4 concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Aminomethyl-4,5-bis(4-methoxyphenyl)thiazole hydrochloride (1.20 g) was added to a mixture of dichloromethane and saturated aqueous sodium hydrogencarbonate, and was extracted with dichloromethane. The separated organic layer was washed with water, and brine, and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and resulting residue was dissolved in dimethylformamide (25 ml). To the reaction mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.71 g) and 3-(tert-butyloxycarbonyl)-4-thiazolidinylcarboxylic acid (0.77 g), and stirred at ambient temperature for 2 hours. The mixture was poured into water, and extracted with ethyl acetate. The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine, and dried over magnesium sulfate and treated with activated charcoal. After filtration, the filtrate was evaporated in vacuo. The residue was subjected to column chromatography on silica gel (50 g) and eluted with a mixture of methanol and chloroform. The fractions containing the object compound were combined and evaporated in vacuo. The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml), and stirred at 2° C. To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml), and stirred at ambient temperature for 1 hour. The resulting residue was evaporated in vacuo. The residue was added iso-propyl ether (50 ml) and stirred at 2° C. for 3 hours. The resulting precipitate was collected by filtration and washed with iso-propyl ether, to give 4,5-bis(4-methoxyphenyl)-2-(4-thiazolidinylcarbonylaminomethyl)thiazole hydrochloride (0.45 g). was extracted with dichloromethane The separated organic layer was washed with water, and brine dried over magnesium sulfate After filtration the filtrate was evaporated in vacuo resulting residue extracted with ethyl acetate The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine dried over magnesium sulfate treated with activated charcoal After filtration the filtrate was evaporated in vacuo eluted with a mixture of methanol and chloroform The fractions containing the object compound evaporated in vacuo The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml) stirred at 2° C To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml) stirred at ambient temperature for 1 hour The resulting residue was evaporated in vacuo The residue was added iso-propyl ether (50 ml) stirred at 2° C. for 3 hours The resulting precipitate was collected by filtration washed with iso-propyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Aminomethyl-4,5-bis(4-methoxyphenyl)thiazole hydrochloride (1.20 g) was added to a mixture of dichloromethane and saturated aqueous sodium hydrogencarbonate, and was extracted with dichloromethane. The separated organic layer was washed with water, and brine, and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and resulting residue was dissolved in dimethylformamide (25 ml). To the reaction mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.71 g) and 3-(tert-butyloxycarbonyl)-4-thiazolidinylcarboxylic acid (0.77 g), and stirred at ambient temperature for 2 hours. The mixture was poured into water, and extracted with ethyl acetate. The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine, and dried over magnesium sulfate and treated with activated charcoal. After filtration, the filtrate was evaporated in vacuo. The residue was subjected to column chromatography on silica gel (50 g) and eluted with a mixture of methanol and chloroform. The fractions containing the object compound were combined and evaporated in vacuo. The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml), and stirred at 2° C. To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml), and stirred at ambient temperature for 1 hour. The resulting residue was evaporated in vacuo. The residue was added iso-propyl ether (50 ml) and stirred at 2° C. for 3 hours. The resulting precipitate was collected by filtration and washed with iso-propyl ether, to give 4,5-bis(4-methoxyphenyl)-2-(4-thiazolidinylcarbonylaminomethyl)thiazole hydrochloride (0.45 g). was extracted with dichloromethane The separated organic layer was washed with water, and brine dried over magnesium sulfate After filtration the filtrate was evaporated in vacuo resulting residue extracted with ethyl acetate The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine dried over magnesium sulfate treated with activated charcoal After filtration the filtrate was evaporated in vacuo eluted with a mixture of methanol and chloroform The fractions containing the object compound evaporated in vacuo The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml) stirred at 2° C To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml) stirred at ambient temperature for 1 hour The resulting residue was evaporated in vacuo The residue was added iso-propyl ether (50 ml) stirred at 2° C. for 3 hours The resulting precipitate was collected by filtration washed with iso-propyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a DMF solution containing 0.10 g of N-(t-butoxy-carbonyl)-1,3-thiazolidine-4-carboxylic acid, 45 μl of tert-butylamine, 66 mg of HOBt and 98 mg of EDC hydrochloride were added under ice cooling and the resultant mixture was stirred for 14 hr. The reaction mixture was treated similarly to that in Example 34 (Process 3) to give 90 mg of the title compound. were added under ice cooling The reaction mixture was treated similarly to that in Example 34 (Process 3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a DMF solution containing 0.10 g of N-(t-butoxy-carbonyl)-1,3-thiazolidine-4-carboxylic acid, 45 μl of tert-butylamine, 66 mg of HOBt and 98 mg of EDC hydrochloride were added under ice cooling and the resultant mixture was stirred for 14 hr. The reaction mixture was treated similarly to that in Example 34 (Process 3) to give 90 mg of the title compound. were added under ice cooling The reaction mixture was treated similarly to that in Example 34 (Process 3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-tert-butoxycarbonylthiazolidine4-carboxylic acid (2.3 g, 10.0 mmol) in THF (30 ml) was added BH3.THF(1.0 M solution in THF, 20.0 ml, 20.0 mmol) at 0° C. After stirred at room temperature for 1.0 h, the reaction mixture was heated under reflux for 1.0 hr. After cooled, the mixture was concentrated in vacuo. Water was added thereto at 0° C., and extracted with EtOAc. The extract was washed with water, then dried over Na2SO4, and concentrated in vacuo to give 3-tert-butoxycarbonyl-5-hydroxymethylthiazolidine (2.0 g , quant) as a a colorless oil. 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.80–2.85 (m, 1H), 3.13–3.17 (m, 1H), 3.20–3.30 (m, 1H), 3.64–3.70 (m, 2H), 4.34 (br s, 1H), 4.60 (br s, 1H). the reaction mixture was heated under reflux for 1.0 hr After cooled the mixture was concentrated in vacuo Water was added at 0° C., and extracted with EtOAc The extract was washed with water dried over Na2SO4 concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-tert-butoxycarbonylthiazolidine4-carboxylic acid (2.3 g, 10.0 mmol) in THF (30 ml) was added BH3.THF(1.0 M solution in THF, 20.0 ml, 20.0 mmol) at 0° C. After stirred at room temperature for 1.0 h, the reaction mixture was heated under reflux for 1.0 hr. After cooled, the mixture was concentrated in vacuo. Water was added thereto at 0° C., and extracted with EtOAc. The extract was washed with water, then dried over Na2SO4, and concentrated in vacuo to give 3-tert-butoxycarbonyl-5-hydroxymethylthiazolidine (2.0 g , quant) as a a colorless oil. 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.80–2.85 (m, 1H), 3.13–3.17 (m, 1H), 3.20–3.30 (m, 1H), 3.64–3.70 (m, 2H), 4.34 (br s, 1H), 4.60 (br s, 1H). the reaction mixture was heated under reflux for 1.0 hr After cooled the mixture was concentrated in vacuo Water was added at 0° C., and extracted with EtOAc The extract was washed with water dried over Na2SO4 concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a DMF solution containing 0.10 g of N-(t-butoxy-carbonyl)-1,3-thiazolidine-4-carboxylic acid, 45 μl of tert-butylamine, 66 mg of HOBt and 98 mg of EDC hydrochloride were added under ice cooling and the resultant mixture was stirred for 14 hr. The reaction mixture was treated similarly to that in Example 34 (Process 3) to give 90 mg of the title compound. were added under ice cooling The reaction mixture was treated similarly to that in Example 34 (Process 3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Aminomethyl-4,5-bis(4-methoxyphenyl)thiazole hydrochloride (1.20 g) was added to a mixture of dichloromethane and saturated aqueous sodium hydrogencarbonate, and was extracted with dichloromethane. The separated organic layer was washed with water, and brine, and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and resulting residue was dissolved in dimethylformamide (25 ml). To the reaction mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.71 g) and 3-(tert-butyloxycarbonyl)-4-thiazolidinylcarboxylic acid (0.77 g), and stirred at ambient temperature for 2 hours. The mixture was poured into water, and extracted with ethyl acetate. The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine, and dried over magnesium sulfate and treated with activated charcoal. After filtration, the filtrate was evaporated in vacuo. The residue was subjected to column chromatography on silica gel (50 g) and eluted with a mixture of methanol and chloroform. The fractions containing the object compound were combined and evaporated in vacuo. The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml), and stirred at 2° C. To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml), and stirred at ambient temperature for 1 hour. The resulting residue was evaporated in vacuo. The residue was added iso-propyl ether (50 ml) and stirred at 2° C. for 3 hours. The resulting precipitate was collected by filtration and washed with iso-propyl ether, to give 4-methoxyphenyl)-2-(4-thiazolidinylcarbonylaminomethyl)thiazole hydrochloride (0.45 g). was extracted with dichloromethane The separated organic layer was washed with water, and brine dried over magnesium sulfate After filtration the filtrate was evaporated in vacuo resulting residue extracted with ethyl acetate The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine dried over magnesium sulfate treated with activated charcoal After filtration the filtrate was evaporated in vacuo eluted with a mixture of methanol and chloroform The fractions containing the object compound evaporated in vacuo The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml) stirred at 2° C To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml) stirred at ambient temperature for 1 hour The resulting residue was evaporated in vacuo The residue was added iso-propyl ether (50 ml) stirred at 2° C. for 3 hours The resulting precipitate was collected by filtration washed with iso-propyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Aminomethyl-4,5-bis(4-methoxyphenyl)thiazole hydrochloride (1.20 g) was added to a mixture of dichloromethane and saturated aqueous sodium hydrogencarbonate, and was extracted with dichloromethane. The separated organic layer was washed with water, and brine, and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and resulting residue was dissolved in dimethylformamide (25 ml). To the reaction mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.71 g) and 3-(tert-butyloxycarbonyl)-4-thiazolidinylcarboxylic acid (0.77 g), and stirred at ambient temperature for 2 hours. The mixture was poured into water, and extracted with ethyl acetate. The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine, and dried over magnesium sulfate and treated with activated charcoal. After filtration, the filtrate was evaporated in vacuo. The residue was subjected to column chromatography on silica gel (50 g) and eluted with a mixture of methanol and chloroform. The fractions containing the object compound were combined and evaporated in vacuo. The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml), and stirred at 2° C. To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml), and stirred at ambient temperature for 1 hour. The resulting residue was evaporated in vacuo. The residue was added iso-propyl ether (50 ml) and stirred at 2° C. for 3 hours. The resulting precipitate was collected by filtration and washed with iso-propyl ether, to give 4,5-bis(4-methoxyphenyl)-2-(4-thiazolidinylcarbonylaminomethyl)thiazole hydrochloride (0.45 g). was extracted with dichloromethane The separated organic layer was washed with water, and brine dried over magnesium sulfate After filtration the filtrate was evaporated in vacuo resulting residue extracted with ethyl acetate The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate, water, and brine dried over magnesium sulfate treated with activated charcoal After filtration the filtrate was evaporated in vacuo eluted with a mixture of methanol and chloroform The fractions containing the object compound evaporated in vacuo The resulting residue (oil-compound) (1.10 g) was dissolved with dichloromethane (20 ml) stirred at 2° C To the reaction mixture was added 1,4-dioxan solution of 4N hydrogen chloride (10 ml) stirred at ambient temperature for 1 hour The resulting residue was evaporated in vacuo The residue was added iso-propyl ether (50 ml) stirred at 2° C. for 3 hours The resulting precipitate was collected by filtration washed with iso-propyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a DMF solution containing 0.10 g of N-(t-butoxy-carbonyl)-1,3-thiazolidine-4-carboxylic acid, 45 μl of tert-butylamine, 66 mg of HOBt and 98 mg of EDC hydrochloride were added under ice cooling and the resultant mixture was stirred for 14 hr. The reaction mixture was treated similarly to that in Example 34 (Process 3) to give 90 mg of the title compound. were added under ice cooling The reaction mixture was treated similarly to that in Example 34 (Process 3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 3-tert-butoxycarbonylthiazolidine4-carboxylic acid (2.3 g, 10.0 mmol) in THF (30 ml) was added BH3.THF(1.0 M solution in THF, 20.0 ml, 20.0 mmol) at 0° C. After stirred at room temperature for 1.0 h, the reaction mixture was heated under reflux for 1.0 hr. After cooled, the mixture was concentrated in vacuo. Water was added thereto at 0° C., and extracted with EtOAc. The extract was washed with water, then dried over Na2SO4, and concentrated in vacuo to give 3-tert-butoxycarbonyl-5-hydroxymethylthiazolidine (2.0 g , quant) as a a colorless oil. 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.80–2.85 (m, 1H), 3.13–3.17 (m, 1H), 3.20–3.30 (m, 1H), 3.64–3.70 (m, 2H), 4.34 (br s, 1H), 4.60 (br s, 1H). the reaction mixture was heated under reflux for 1.0 hr After cooled the mixture was concentrated in vacuo Water was added at 0° C., and extracted with EtOAc The extract was washed with water dried over Na2SO4 concentrated in vacuo