4-bromobenzenecarbothioamide

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

実験手順: To a stirring solution of 2-bromo-1-(4-(heptyloxy)phenyl)ethanone INT-4 (1.37 g, 4.38 mmol) in EtOH (10 mL) were added 4-bromobenzothioamide (0.95 g, 4.38 mmol) and isopropanol (10 mL). The reaction mixture was stirred at RT for 16 h. The solid was isolated by filtration, washed with EtOH (5 mL) then taken up in DCM (10 mL) and NaHCO3 (20 mL) and stirred for 1 h at RT. The solid was isolated by filtration, washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried to afford 1.02 g (52%) of 2-(4-bromophenyl)-4-(4-(heptyloxy)phenyl)thiazole as a white micro-crystalline solid. LCMS-ESI (m/z) calculated for C22H24BrNOS: 429.1. found 430.0 [M+H]+, tR=3.20 min. (Method 4). The solid was isolated by filtration washed with EtOH (5 mL) NaHCO3 (20 mL) and stirred for 1 h at RT The solid was isolated by filtration washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Fifty ml. of dioxane was used to dissolve 7.43 g. (0.034 mole) of 4-bromothiobenzamide with heating to about 60° C. Then 10.0 g. (0.034 mole) of 4,4'-dimethoxydesyl chloride in 50 ml. of dioxane was added and the mixture was heated to 100° C. for two hours. The mixture was cooled and acidified with 1 N hydrochloric acid. Most of the dioxane was removed in vacuo and the solid formed was filtered. The solid was purified by silica gel chromatography (400 g.), using benzene as the eluting agent. The product had a melting point of about 155°-157° C. and weighed 8.83 g. (57% yield). The mass spectrum showed the expected molecular ions at m/e=451 and 453. to dissolve 7.43 g The mixture was cooled Most of the dioxane was removed in vacuo the solid formed was filtered The solid was purified by silica gel chromatography (400 g.)

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

実験手順: To a stirring solution of 2-bromo-1-(4-(heptyloxy)phenyl)ethanone INT-4 (1.37 g, 4.38 mmol) in EtOH (10 mL) were added 4-bromobenzothioamide (0.95 g, 4.38 mmol) and isopropanol (10 mL). The reaction mixture was stirred at room temperature for 16 h. The solid was isolated by filtration, washed with EtOH (5 mL) then taken up in DCM (10 mL) and NaHCO3 (20 mL) and stirred for 1 h at room temperature. The solid was isolated by filtration, washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried to afford 1.02 g (52%) of 2-(4-bromophenyl)-4-(4-(heptyloxy)phenyl)thiazole as a white micro-crystalline solid. LCMS-ESI (m/z) calculated for C22H24BrNOS: 429.1. found 430.0 [M+H]+, tR=3.20 min. (Method 4). The solid was isolated by filtration washed with EtOH (5 mL) NaHCO3 (20 mL) and stirred for 1 h at room temperature The solid was isolated by filtration washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried

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

実験手順: A mixture of 4-bromothiobenzamide (2.16 g., 0.01 mole) and 6-chloro-5-oxohexanenitrile (2.28 g., 0.012 mole) is heated at 60° C. in toluene for 12 hours. On cooling and partial evaporation, there is obtained 3-[2-(4-bromophenyl)thiazol-4-yl]butanenitrile. On cooling partial evaporation

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

実験手順: A mixture of 4-bromothiobenzamide (2.16 g., 0.01 mole) and ethyl 3-bromo-4-oxobutyrate (3.2 g., 0.015 mole) in ethanol (50 ml.) is heated at reflux for 6 hours. On cooling and partial evaporation there is obtained 2-(4-bromophenyl)thiazol-5-ylacetic acid ethyl ester. Reaction of this product with ammonia according to the procedure of Example 3 gives 2-(4-bromophenyl)thiazol-5-ylacetamide, which on reaction with diethyl oxalate and base in dimethylformamide, according to the general procedure of Example 6, affords the title compound. is heated at reflux for 6 hours On cooling partial evaporation there

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

実験手順: A mixture of 4-bromothiobenzamide (7.62 g, 35.2 mmole), ethyl 4-chloroacetoacetate (5.82 g, 35.2 mmole) and dimethylformamide (23 ml) was stirred under nitrogen and heated in an oil-bath at 115°-120° C. for 11/2 hours. Thin layer chromatography showed the presence of unreacted thioamide. More ethyl chloroacetoacetate (2.91 g, 17.6 mmole) was added and heating was continued for 11/2 hours, by which time no unreacted thioamide remained. The mixture was cooled and poured into ice-water (125 ml) and extracted with ether (2×100 ml). The extract was washed with water (2×100 ml), dried (MgSO4) and evaporated to a semi-solid which contained the desired ester and the corresponding acid. The mixture was dissolved in ethanol (100 ml) saturated with hydrogen chloride and the solution was allowed to stand at room temperature for 1 day. The solution was evaporated to dryness and the ester was used without further purification for preparing the amide. heated in an oil-bath at 115°-120° C. for 11/2 hours heating 2 hours The mixture was cooled extracted with ether (2×100 ml) The extract was washed with water (2×100 ml) dried (MgSO4) evaporated to a semi-solid which The mixture was dissolved in ethanol (100 ml) saturated with hydrogen chloride The solution was evaporated to dryness the ester was used without further purification for preparing the amide

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

実験手順: To a stirring solution of 2-bromo-1-(4-(heptyloxy)phenyl)ethanone INT-4 (1.37 g, 4.38 mmol) in EtOH (10 mL) were added 4-bromobenzothioamide (0.95 g, 4.38 mmol) and isopropanol (10 mL). The reaction mixture was stirred at RT for 16 h. The solid was isolated by filtration, washed with EtOH (5 mL) then taken up in DCM (10 mL) and NaHCO3 (20 mL) and stirred for 1 h at RT. The solid was isolated by filtration, washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried to afford 1.02 g (52%) of 2-(4-bromophenyl)-4-(4-(heptyloxy)phenyl)thiazole as a white micro-crystalline solid. LCMS-ESI (m/z) calculated for C22H24BrNOS: 429.1; found 430.0 [M+H]+, tR=3.20 min. (Method 4). The solid was isolated by filtration washed with EtOH (5 mL) NaHCO3 (20 mL) and stirred for 1 h at RT The solid was isolated by filtration washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried

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

実験手順: A mixture of 4-bromothiobenzamide (2.16 g., 0.01 mole) and 6-chloro-5-oxohexanenitrile (2.28 g., 0.012 mole) is heated at 60° C. in toluene for 12 hours. On cooling and partial evaporation, there is obtained 3-[2-(4-bromophenyl)thiazol-4-yl]butanenitrile. On cooling partial evaporation

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

実験手順: A mixture of 4-bromothiobenzamide (2.16 g., 0.01 mole) and ethyl 3-bromo-4-oxobutyrate (3.2 g., 0.015 mole) in ethanol (50 ml.) is heated at reflux for 6 hours. On cooling and partial evaporation there is obtained 2-(4-bromophenyl)thiazol-5-ylacetic acid ethyl ester. Reaction of this product with ammonia according to the procedure of Example 3 gives 2-(4-bromophenyl)thiazol-5-ylacetamide, which on reaction with diethyl oxalate and base in dimethylformamide, according to the general procedure of Example 6, affords the title compound. is heated at reflux for 6 hours On cooling partial evaporation there

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

実験手順: A mixture of 4-bromothiobenzamide (7.62 g), 35.2 mmole), ethyl 4-chloroacetoacetate (5.82 g, 35.2 mmole) and dimethylformamide (23 ml) was stirred under nitrogen and heated in an oil-bath at 115°-120° C. for 11/2 hours. Thin layer chromatography showed the presence of unreacted thioamide. More ethyl chloroacetoacetate (2.91 g, 17.6 mmole) was added and heating was continued for 11/2 hours, by which time no unreacted thioamide remained. The mixture was cooled and poured into ice-water (125 ml) and extracted with ether (2×100 ml). The extract was washed with water (2×100 ml), dried (MgSO4) and evaporated to a semi-solid which contained the desired ester and the corresponding acid. The mixture was dissolved in ethanol (100 ml) saturated with hydrogen chloride and the solution was allowed to stand at room temperature for 1 day. The solution was evaporated to dryness and the ester was used without further purification for preparing the amide. heated in an oil-bath at 115°-120° C. for 11/2 hours heating 2 hours The mixture was cooled extracted with ether (2×100 ml) The extract was washed with water (2×100 ml) dried (MgSO4) evaporated to a semi-solid which The mixture was dissolved in ethanol (100 ml) saturated with hydrogen chloride The solution was evaporated to dryness the ester was used without further purification for preparing the amide

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

実験手順: To a stirring solution of 2-bromo-1-(4-(heptyloxy)phenyl)ethanone INT-4 (1.37 g, 4.38 mmol) in EtOH (10 mL) were added 4-bromobenzothioamide (0.95 g, 4.38 mmol) and isopropanol (10 mL). The reaction mixture was stirred at RT for 16 h. The solid was isolated by filtration, washed with EtOH (5 mL) then taken up in DCM (10 mL) and NaHCO3 (20 mL) and stirred for 1 h at RT. The solid was isolated by filtration, washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried to afford 1.02 g (52%) of 2-(4-bromophenyl)-4-(4-(heptyloxy)phenyl)thiazole as a white micro-crystalline solid. LCMS-ESI (m/z) calculated for C22H24BrNOS: 429.1. found 430.0 [M+H]+, tR=3.20 min. (Method 4). The solid was isolated by filtration washed with EtOH (5 mL) NaHCO3 (20 mL) and stirred for 1 h at RT The solid was isolated by filtration washed with water (2×10 mL) and acetonitrile (2×4 mL) then dried