1,3-DIHYDRO-2H-INDOLE-2-THIONE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: One liter of triethylamine is added slowly in the course of 2 hours 30 minutes to a vigorously stirred suspension of 194 g (1.3 mol) of 2-indolinethione (prepared according to Y. Nakisumi and Coll. Chem. Pharm. Bull. 1984, 32, (3), 877) in 108 g (1.5 mol) of acrylic acid. The mixture is brought to reflux for 12 hours while stirring is maintained, and then cooled and concentrated under vacuum. The residue is taken up with 10% strength aqueous sodium bicarbonate solution and the mixture is filtered. The filtrate is acidified with aqueous hydrochloric acid solution. The precipitate formed is drained, washed with water and dried. It is recrystallized in toluene. to reflux for 12 hours is maintained cooled concentrated under vacuum the mixture is filtered The precipitate formed washed with water dried It is recrystallized in toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a solution of 1,3-dihydroindol-2-thione (19.7 g) and ethyl 2-bromo-2-phenylpropionate (33.9 g) indimethylformamide (DMF, 200 ml), an aqueous 2 N sodium hydroxide solution (66 ml) was added dropwise under ice cooling, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water, and was extracted with ethyl acetate. The organic layer was washed with water, and then with saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. n-Hexane was added to the evaporation residue to cause crystallization. The resulting crystalline matter was recrystallized from ethyl acetate/n-hexane to give 30.3 g (yield: 71%) of product compound as a pale yellow crystal form. The melting point was 97°-99° C. was extracted with ethyl acetate The organic layer was washed with water with saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure n-Hexane was added to the evaporation residue crystallization The resulting crystalline matter was recrystallized from ethyl acetate/n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a solution of 1,3-dihydroindol-2-thione (19.7 g) and ethyl 2-bromo-2-phenylpropionate (33.9 g) indimethylformamide (DMF, 200 ml), an aqueous 2 N sodium hydroxide solution (66 ml) was added dropwise under ice cooling, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water, and was extracted with ethyl acetate. The organic layer was washed with water, and then with saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. n-Hexane was added to the evaporation residue to cause crystallization. The resulting crystalline matter was recrystallized from ethyl acetate/n-hexane to give 30.3 g (yield: 71%) of product compound as a pale yellow crystal form. The melting point was 97°-99° C. was extracted with ethyl acetate The organic layer was washed with water with saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure n-Hexane was added to the evaporation residue crystallization The resulting crystalline matter was recrystallized from ethyl acetate/n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-indolinthione (7.45 g) in acetone (75 ml) is added potassium carbonate (7.60 g). After stirring, 4-chloro-2-butyn-1-ol (5.48 g) is added thereto. The mixture is stirred at room temperature for 5 hours and filtered. The filtrate is condensed to remove the acetone completely. The residue is dissolved into diethylamine (10 ml), kept at room temperature for 1 hour and evaporated to remove the diethylamine aiming to remove excessive agents. The residue is dissolved in ether (250 ml), washed with water, 2 N hydrochloric acid, water and a saturated saline solution successively, dried and evaporated to give the title compound as an oil (12.0 g). The mixture is stirred at room temperature for 5 hours filtered condensed to remove the acetone completely The residue is dissolved into diethylamine (10 ml) evaporated to remove the diethylamine aiming to remove excessive agents The residue is dissolved in ether (250 ml) washed with water, 2 N hydrochloric acid, water a saturated saline solution successively, dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the product (14.9 g) of the above (1) in acetone (250 ml) are added potassium carbonate (16.5 g) and propargyl bromide (14.3 g) successively and the mixture is stirred at room temperature for three hours. The precipitate is filtered off. The filtrate is condensed and extracted with ether after addition of water. The extract is washed with water, dried and evaporated to remove the solvent yielding an oily residue (23 g). The residue is chromatographed on a column of silica gel (100 g) and eluted with benzene-hexane. The eluate is condensed to give the tile compound as an oil (18.3 g). Yield: 98% The precipitate is filtered off condensed extracted with ether after addition of water The extract is washed with water dried evaporated to remove the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-indolinthione (7.45 g) in acetone (75 ml) is added potassium carbonate (7.60 g). After stirring, 4-chloro-2-butyn-1-ol (5.48 g) is added thereto. The mixture is stirred at room temperature for 5 hours and filtered. The filtrate is condensed to remove the acetone completely. The residue is dissolved into diethylamine (10 ml), kept at room temperature for 1 hour and evaporated to remove the diethylamine aiming to remove excessive agents. The residue is dissolved in ether (250 ml), washed with water, 2 N hydrochloric acid, water and a saturated saline solution successively, dried and evaporated to give the title compound as an oil (12.0 g). The mixture is stirred at room temperature for 5 hours filtered condensed to remove the acetone completely The residue is dissolved into diethylamine (10 ml) evaporated to remove the diethylamine aiming to remove excessive agents The residue is dissolved in ether (250 ml) washed with water, 2 N hydrochloric acid, water a saturated saline solution successively, dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the product (14.9 g) of the above (1) in acetone (250 ml) are added potassium carbonate (16.5 g) and propargyl bromide (14.3 g) successively and the mixture is stirred at room temperature for three hours. The precipitate is filtered off. The filtrate is condensed and extracted with ether after addition of water. The extract is washed with water, dried and evaporated to remove the solvent yielding an oily residue (23 g). The residue is chromatographed on a column of silica gel (100 g) and eluted with benzene-hexane. The eluate is condensed to give the tile compound as an oil (18.3 g). Yield: 98% The precipitate is filtered off condensed extracted with ether after addition of water The extract is washed with water dried evaporated to remove the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: One liter of triethylamine is added slowly in the course of 2 hours 30 minutes to a vigorously stirred suspension of 194 g (1.3 mol) of 2-indolinethione (prepared according to Y. Nakisumi and Coll. Chem. Pharm. Bull. 1984, 32, (3), 877) in 108 g (1.5 mol) of acrylic acid. The mixture is brought to reflux for 12 hours while stirring is maintained, and then cooled and concentrated under vacuum. The residue is taken up with 10% strength aqueous sodium bicarbonate solution and the mixture is filtered. The filtrate is acidified with aqueous hydrochloric acid solution. The precipitate formed is drained, washed with water and dried. It is recrystallized in toluene. to reflux for 12 hours is maintained cooled concentrated under vacuum the mixture is filtered The precipitate formed washed with water dried It is recrystallized in toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a solution of 1,3-dihydroindol-2-thione (19.7 g) and ethyl 2-bromo-2-phenylpropionate (33.9 g) indimethylformamide (DMF, 200 ml), an aqueous 2 N sodium hydroxide solution (66 ml) was added dropwise under ice cooling, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water, and was extracted with ethyl acetate. The organic layer was washed with water, and then with saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. n-Hexane was added to the evaporation residue to cause crystallization. The resulting crystalline matter was recrystallized from ethyl acetate/n-hexane to give 30.3 g (yield: 71%) of product compound as a pale yellow crystal form. The melting point was 97°-99° C. was extracted with ethyl acetate The organic layer was washed with water with saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure n-Hexane was added to the evaporation residue crystallization The resulting crystalline matter was recrystallized from ethyl acetate/n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-indolinthione (7.45 g) in acetone (75 ml) is added potassium carbonate (7.60 g). After stirring, 4-chloro-2-butyn-1-ol (5.48 g) is added thereto. The mixture is stirred at room temperature for 5 hours and filtered. The filtrate is condensed to remove the acetone completely. The residue is dissolved into diethylamine (10 ml), kept at room temperature for 1 hour and evaporated to remove the diethylamine aiming to remove excessive agents. The residue is dissolved in ether (250 ml), washed with water, 2 N hydrochloric acid, water and a saturated saline solution successively, dried and evaporated to give the title compound as an oil (12.0 g). The mixture is stirred at room temperature for 5 hours filtered condensed to remove the acetone completely The residue is dissolved into diethylamine (10 ml) evaporated to remove the diethylamine aiming to remove excessive agents The residue is dissolved in ether (250 ml) washed with water, 2 N hydrochloric acid, water a saturated saline solution successively, dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the product (14.9 g) of the above (1) in acetone (250 ml) are added potassium carbonate (16.5 g) and propargyl bromide (14.3 g) successively and the mixture is stirred at room temperature for three hours. The precipitate is filtered off. The filtrate is condensed and extracted with ether after addition of water. The extract is washed with water, dried and evaporated to remove the solvent yielding an oily residue (23 g). The residue is chromatographed on a column of silica gel (100 g) and eluted with benzene-hexane. The eluate is condensed to give the tile compound as an oil (18.3 g). Yield: 98% The precipitate is filtered off condensed extracted with ether after addition of water The extract is washed with water dried evaporated to remove the solvent