4,4-dimethylpentane-1-sulfonamide

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

実験手順: Anhydrous ammonia gas was passed into a solution of 4,4-dimethylpentane sulphonyl chloride (1.85 g) in dry tetrahydrofuran (5 ml) at 5-10° C. until saturation. The resulting suspension was stirred at room temperature for 18 hours and then evaporated under reduced pressure. The residue was partitioned between ethyl acetate (20 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 20 ml), dried (Na2SO4) and evaporated. Column chromatography on silica eluting with dichloromethane:methanol 98:2 gave 4,4-dimethylpentane sulphonic acid amide as an off-white solid (0.72 g). evaporated under reduced pressure The residue was partitioned between ethyl acetate (20 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 20 ml) dried (Na2SO4) evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Caesium carbonate (2.62 g) was added to a solution of 4,4-dimethylpentane-1-sulphonic acid amide (720 mg) and 4,6-dichloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)-pyrimidine (Can. Pat. Appl. 2071193) (1.40 g) in dry N,N-dimethyl formamide (8 ml) and the resulting mixture stirred at 80° C. for 4 hours under nitrogen. The reaction mixture was allowed to cool and then partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 2×20 ml), dried (Na2SO4) and evaporated under reduced pressure. Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate:pentane to give N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-4,4-dimethyl-1-pentanesulfonamide as a white solid (1.08 g). to cool partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 2×20 ml) dried (Na2SO4) evaporated under reduced pressure Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate

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

実験手順: Anhydrous ammonia gas was passed into a solution of 4,4-dimethylpentane sulphonyl chloride (1.85 g) in dry tetrahydrofuran (5 ml) at 5-10° C. until saturation. The resulting suspension was stirred at room temperature for 18 hours and then evaporated under reduced pressure. The residue was partitioned between ethyl acetate (20 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 20 ml), dried (Na2SO4) and evaporated. Column chromatography on silica eluting with dichloromethane:methanol 98:2 gave 4,4-dimethylpentane sulphonic acid amide as an off-white solid (0.72 g). evaporated under reduced pressure The residue was partitioned between ethyl acetate (20 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 20 ml) dried (Na2SO4) evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Caesium carbonate (2.62 g) was added to a solution of 4,4-dimethylpentane-1-sulphonic acid amide (720 mg) and 4,6-dichloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)-pyrimidine (Can. Pat. Appl. 2071193) (1.40 g) in dry N,N-dimethyl formamide (8 ml) and the resulting mixture stirred at 80° C. for 4 hours under nitrogen. The reaction mixture was allowed to cool and then partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 2×20 ml), dried (Na2SO4) and evaporated under reduced pressure. Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate:pentane to give N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-4,4-dimethyl-1-pentanesulfonamide as a white solid (1.08 g). to cool partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 2×20 ml) dried (Na2SO4) evaporated under reduced pressure Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Caesium carbonate (2.62 g) was added to a solution of 4,4-dimethylpentane-1-sulphonic acid amide (720 mg) and 4,6-dichloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)-pyrimidine (Can. Pat. Appl. 2071193) (1.40 g) in dry N,N-dimethyl formamide (8 ml) and the resulting mixture stirred at 80° C. for 4 hours under nitrogen. The reaction mixture was allowed to cool and then partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 2×20 ml), dried (Na2SO4) and evaporated under reduced pressure. Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate:pentane to give N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-4,4-dimethyl-1-pentanesulfonamide as a white solid (1.08 g). to cool partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 2×20 ml) dried (Na2SO4) evaporated under reduced pressure Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate

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

実験手順: Anhydrous ammonia gas was passed into a solution of 4,4-dimethylpentane sulphonyl chloride (1.85 g) in dry tetrahydrofuran (5 ml) at 5-10° C. until saturation. The resulting suspension was stirred at room temperature for 18 hours and then evaporated under reduced pressure. The residue was partitioned between ethyl acetate (20 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 20 ml), dried (Na2SO4) and evaporated. Column chromatography on silica eluting with dichloromethane:methanol 98:2 gave 4,4-dimethylpentane sulphonic acid amide as an off-white solid (0.72 g). evaporated under reduced pressure The residue was partitioned between ethyl acetate (20 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 20 ml) dried (Na2SO4) evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Caesium carbonate (2.62 g) was added to a solution of 4,4-dimethylpentane-1-sulphonic acid amide (720 mg) and 4,6-dichloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)-pyrimidine (Can. Pat. Appl. 2071193) (1.40 g) in dry N,N-dimethyl formamide (8 ml) and the resulting mixture stirred at 80° C. for 4 hours under nitrogen. The reaction mixture was allowed to cool and then partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml). The organic phase was separated, washed (brine 2×20 ml), dried (Na2SO4) and evaporated under reduced pressure. Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate:pentane to give N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-4,4-dimethyl-1-pentanesulfonamide as a white solid (1.08 g). to cool partitioned between ethyl acetate (40 ml) and 2N aqueous hydrochloric acid (20 ml) The organic phase was separated washed (brine 2×20 ml) dried (Na2SO4) evaporated under reduced pressure Column chromatography on silica eluting with a solvent gradient of dichloromethane:methanol 100:0 changing to 99:1 gave crude product which was recrystallised from ethyl acetate