2-chloro-5-iodoaniline

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: 2-Chloro-5-iodoaniline (630 mg, 2.49 mmol) was heated at reflux in acetic acid (7 ml) and acetic anhydride (7 ml) for 18 hours. The solution was concentrated in vacuo, azeotroping with toluene. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase separated and washed with saturated aqueous sodium bicarbonate solution, water, brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford a mixture of the mono- and di-acylated acetamide (N-(2-chloro-5-iodophenyl)acetamide and N-acetyl-N-(2-chloro-5-iodophenyl)acetamide). To this product (820 mg) in 1,4-dioxane (12 ml) was added cis-2,6-dimethyl piperazine (416 mg, 3.64 mmol), sodium tert-butoxide (700 mg, 7.29 mmol), tris(dibenzylideneacetone)dipalladium(0) (45 mg, 0.049 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (39 mg, 0.098 mmol) and the reaction heated at reflux for 18 hours under argon. The reaction mixture was cooled, diluted with ethyl acetate (30 ml) and stirred with a mixture of celite and charcoal. The solution was filtered through celite washing with ethyl acetate. The filtrate was concentrated in vacuo, and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was washed with water, 50% saturated brine solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was treated with 5N HCl (20 ml) and heated at reflux for 24 hours under argon. The reaction was cooled, and the solution washed with ethyl acetate (×3), poured onto ice, basified with 0.880 ammonia and extracted with dichloromethane (×4). The combined extracts were washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (gradient of 2% to 10% methanol in dichloromethane) to afford the title compound (D34). MS (ES+) m/e 240/242 [M+H]+. The solution was concentrated in vacuo azeotroping with toluene The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic phase separated washed with saturated aqueous sodium bicarbonate solution, water, brine dried over anhydrous magnesium sulfate concentrated in vacuo to afford the reaction heated at reflux for 18 hours under argon The reaction mixture was cooled The solution was filtered through celite washing with ethyl acetate The filtrate was concentrated in vacuo the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic phase was washed with water, 50% saturated brine solution, brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was treated with 5N HCl (20 ml) heated at reflux for 24 hours under argon The reaction was cooled the solution washed with ethyl acetate (×3) poured onto ice extracted with dichloromethane (×4) The combined extracts were washed with water, brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was purified by chromatography on silica gel (gradient of 2% to 10% methanol in dichloromethane)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-chloro-4-iodo-2-nitrobenzene (1.27 g, 4.49 mmol) in methanol (20 ml) was added iron powder (1.25 g, 22 mmol) and the reaction heated to 50° C. A solution of ammonium chloride (1.92 g, 36 mmol) in water (10 ml) was added slowly and the reaction heated to 70° C. overnight. Reaction was cooled, filtered through celite, washed with methanol and solvent reduced in vacuo. The residue was purified by chromatography on silica gel (gradient of hexane to 10% ethyl acetate in hexane) to afford the title compound. MS (ES+) m/e 254 [M+H]+. the reaction heated to 70° C. overnight Reaction was cooled filtered through celite washed with methanol and solvent The residue was purified by chromatography on silica gel (gradient of hexane to 10% ethyl acetate in hexane)

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

実験手順: 2-Chloro-5-iodoaniline (630 mg, 2.49 mmol) was heated at reflux in acetic acid (7 ml) and acetic anhydride (7 ml) for 18 hours. The solution was concentrated in vacuo, azeotroping with toluene. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase separated and washed with saturated aqueous sodium bicarbonate solution, water, brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford a mixture of the mono- and di-acylated acetamide (N-(2-chloro-5-iodophenyl)acetamide and N-acetyl-N-(2-chloro-5-iodophenyl)acetamide). To this product (820 mg) in 1,4-dioxane (12 ml) was added cis-2,6-dimethyl piperazine (416 mg, 3.64 mmol), sodium tert-butoxide (700 mg, 7.29 mmol), tris(dibenzylideneacetone)dipalladium(0) (45 mg, 0.049 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (39 mg, 0.098 mmol) and the reaction heated at reflux for 18 hours under argon. The reaction mixture was cooled, diluted with ethyl acetate (30 ml) and stirred with a mixture of celite and charcoal. The solution was filtered through celite washing with ethyl acetate. The filtrate was concentrated in vacuo, and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was washed with water, 50% saturated brine solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was treated with 5N HCl (20 ml) and heated at reflux for 24 hours under argon. The reaction was cooled, and the solution washed with ethyl acetate (×3), poured onto ice, basified with 0.880 ammonia and extracted with dichloromethane (×4). The combined extracts were washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (gradient of 2% to 10% methanol in dichloromethane) to afford the title compound (D34). MS (ES+) m/e 240/242 [M+H]+. The solution was concentrated in vacuo azeotroping with toluene The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic phase separated washed with saturated aqueous sodium bicarbonate solution, water, brine dried over anhydrous magnesium sulfate concentrated in vacuo to afford the reaction heated at reflux for 18 hours under argon The reaction mixture was cooled The solution was filtered through celite washing with ethyl acetate The filtrate was concentrated in vacuo the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic phase was washed with water, 50% saturated brine solution, brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was treated with 5N HCl (20 ml) heated at reflux for 24 hours under argon The reaction was cooled the solution washed with ethyl acetate (×3) poured onto ice extracted with dichloromethane (×4) The combined extracts were washed with water, brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was purified by chromatography on silica gel (gradient of 2% to 10% methanol in dichloromethane)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-chloro-4-iodo-2-nitrobenzene (1.27 g, 4.49 mmol) in methanol (20 ml) was added iron powder (1.25 g, 22 mmol) and the reaction heated to 50° C. A solution of ammonium chloride (1.92 g, 36 mmol) in water (10 ml) was added slowly and the reaction heated to 70° C. overnight. Reaction was cooled, filtered through celite, washed with methanol and solvent reduced in vacuo. The residue was purified by chromatography on silica gel (gradient of hexane to 10% ethyl acetate in hexane) to afford the title compound. MS (ES+) m/e 254 [M+H]+. the reaction heated to 70° C. overnight Reaction was cooled filtered through celite washed with methanol and solvent The residue was purified by chromatography on silica gel (gradient of hexane to 10% ethyl acetate in hexane)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon, 12.62 g (316.16 mmol, 60% in mineral oil) of sodium hydride were suspended in 250 ml of abs. DMF and cooled to 0° C. 32 g (126.3 mmol) of 2-chloro-5-iodoaniline, dissolved in 80 ml of abs. DMF, were then slowly added dropwise, and the mixture was stirred at 0° C. for 30 min. 41 ml (303 mmol) of 1-(chloromethyl)-4-methoxybenzene were then slowly added to the reaction mixture, and the mixture was subsequently warmed to room temperature. The mixture was stirred at RT overnight and then carefully poured into 150 ml of ice-water. The organic phase was separated off, and the aqueous phase was then extracted three more times with diethyl ether. The combined organic phases were dried over magnesium sulphate. After filtration, the solvent was removed under reduced pressure. The crude product obtained was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1). This gave 59 g of the title compound (94% of theory). the mixture was subsequently warmed to room temperature The mixture was stirred at RT overnight The organic phase was separated off the aqueous phase was then extracted three more times with diethyl ether The combined organic phases were dried over magnesium sulphate After filtration the solvent was removed under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon, 12.62 g (316.16 mmol, 60% in mineral oil) of sodium hydride were suspended in 250 ml of abs. DMF and cooled to 0° C. 32 g (126.3 mmol) of 2-chloro-5-iodoaniline, dissolved in 80 ml of abs. DMF, were then slowly added dropwise, and the mixture was stirred at 0° C. for 30 min. 41 ml (303 mmol) of 1-(chloromethyl)-4-methoxybenzene were then slowly added to the reaction mixture, and the mixture was subsequently warmed to room temperature. The mixture was stirred at RT overnight and then carefully poured into 150 ml of ice-water. The organic phase was separated off, and the aqueous phase was then extracted three more times with diethyl ether. The combined organic phases were dried over magnesium sulphate. After filtration, the solvent was removed under reduced pressure. The crude product obtained was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1). This gave 59 g of the title compound (94% of theory). the mixture was subsequently warmed to room temperature The mixture was stirred at RT overnight The organic phase was separated off the aqueous phase was then extracted three more times with diethyl ether The combined organic phases were dried over magnesium sulphate After filtration the solvent was removed under reduced pressure

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

実験手順: 2-Chloro-5-iodoaniline (630 mg, 2.49 mmol) was heated at reflux in acetic acid (7 ml) and acetic anhydride (7 ml) for 18 hours. The solution was concentrated in vacuo, azeotroping with toluene. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase separated and washed with saturated aqueous sodium bicarbonate solution, water, brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford a mixture of the mono- and di-acylated acetamide (N-(2-chloro-5-iodophenyl)acetamide and N-acetyl-N-(2-chloro-5-iodophenyl)acetamide). To this product (820 mg) in 1,4-dioxane (12 ml) was added cis-2,6-dimethyl piperazine (416 mg, 3.64 mmol), sodium tert-butoxide (700 mg, 7.29 mmol), tris(dibenzylideneacetone)dipalladium(0) (45 mg, 0.049 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (39 mg, 0.098 mmol) and the reaction heated at reflux for 18 hours under argon. The reaction mixture was cooled, diluted with ethyl acetate (30 ml) and stirred with a mixture of celite and charcoal. The solution was filtered through celite washing with ethyl acetate. The filtrate was concentrated in vacuo, and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was washed with water, 50% saturated brine solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was treated with 5N HCl (20 ml) and heated at reflux for 24 hours under argon. The reaction was cooled, and the solution washed with ethyl acetate (×3), poured onto ice, basified with 0.880 ammonia and extracted with dichloromethane (×4). The combined extracts were washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (gradient of 2% to 10% methanol in dichloromethane) to afford the title compound (D34). MS (ES+) m/e 240/242 [M+H]+. The solution was concentrated in vacuo azeotroping with toluene The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic phase separated washed with saturated aqueous sodium bicarbonate solution, water, brine dried over anhydrous magnesium sulfate concentrated in vacuo to afford the reaction heated at reflux for 18 hours under argon The reaction mixture was cooled The solution was filtered through celite washing with ethyl acetate The filtrate was concentrated in vacuo the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic phase was washed with water, 50% saturated brine solution, brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was treated with 5N HCl (20 ml) heated at reflux for 24 hours under argon The reaction was cooled the solution washed with ethyl acetate (×3) poured onto ice extracted with dichloromethane (×4) The combined extracts were washed with water, brine dried over anhydrous sodium sulfate concentrated in vacuo The residue was purified by chromatography on silica gel (gradient of 2% to 10% methanol in dichloromethane)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-chloro-4-iodo-2-nitrobenzene (1.27 g, 4.49 mmol) in methanol (20 ml) was added iron powder (1.25 g, 22 mmol) and the reaction heated to 50° C. A solution of ammonium chloride (1.92 g, 36 mmol) in water (10 ml) was added slowly and the reaction heated to 70° C. overnight. Reaction was cooled, filtered through celite, washed with methanol and solvent reduced in vacuo. The residue was purified by chromatography on silica gel (gradient of hexane to 10% ethyl acetate in hexane) to afford the title compound. MS (ES+) m/e 254 [M+H]+. the reaction heated to 70° C. overnight Reaction was cooled filtered through celite washed with methanol and solvent The residue was purified by chromatography on silica gel (gradient of hexane to 10% ethyl acetate in hexane)