2-甲基-1,4-氧氮杂环庚烷盐酸盐

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

实验步骤: To a slurry of 2-Chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (126 mg, 0.565 mmol) and 2-methyl-[1,4]oxazepane hydrochloride (100 mg, 0.660 mmol) was added triethylamine (172 mg, 1.70 mmol) at room temperature. The resulting mixture was stirred at room temperature for 10 hours and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant; ethyl acetate) to afford 1-methyl-2-(2-methyl-[1,4]oxazepan-4-yl)-1H-[4,4′]bipyrimidinyl-6-one as white solid (A051) (103 mg, 61%). partitioned between water and ethyl acetate The organic layer was washed with brine dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel column chromatography (eluant; ethyl acetate)

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

实验步骤: To a solution of 4-(4-methoxy-benzyl)-2-methyl-[1,4]oxazepane (1.66 g, 7.05 mmol) in 1,2-dichloroethane (12 ml) was added 1-chloroethyl chloroformate (2.52 g, 17.6 mmol) at room temperature. The mixture was refluxed for 5 hours and cooled to room temperature. After the addition of methanol (15 ml), the mixture was refluxed for 3 hours and concentrated in vacuo to afford the crude product. This crude product was partitioned between ether and 1N hydrochloric acid, and washed with ether. The water phase was basified with saturated aqueous sodium hydrogen carbonate. The product was extracted with dichloromethane. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure carefully to avoid evaporating the product. To the resulting solution was added 4N hydrochloric acid in ethyl acetate. The solution was concentrated in vacuo to afford 2-methyl-[1,4]oxazepane hydrochloride as pale yellow oil (964 mg, 90%). The mixture was refluxed for 5 hours the mixture was refluxed for 3 hours concentrated in vacuo to afford the crude product This crude product was partitioned between ether and 1N hydrochloric acid washed with ether The product was extracted with dichloromethane The organic layer was dried over sodium sulfate the solvent was removed under reduced pressure carefully to avoid evaporating the product To the resulting solution was added 4N hydrochloric acid in ethyl acetate The solution was 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 slurry of 2-Chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (126 mg, 0.565 mmol) and 2-methyl-[1,4]oxazepane hydrochloride (100 mg, 0.660 mmol) was added triethylamine (172 mg, 1.70 mmol) at room temperature. The resulting mixture was stirred at room temperature for 10 hours and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant; ethyl acetate) to afford 1-methyl-2-(2-methyl-[1,4]oxazepan-4-yl)-1H-[4,4′]bipyrimidinyl-6-one as white solid (A051) (103 mg, 61%). partitioned between water and ethyl acetate The organic layer was washed with brine dried over sodium sulfate concentrated in vacuo The residue was purified by silica gel column chromatography (eluant; ethyl acetate)

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

实验步骤: To a solution of 4-(4-methoxy-benzyl)-2-methyl-[1,4]oxazepane (1.66 g, 7.05 mmol) in 1,2-dichloroethane (12 ml) was added 1-chloroethyl chloroformate (2.52 g, 17.6 mmol) at room temperature. The mixture was refluxed for 5 hours and cooled to room temperature. After the addition of methanol (15 ml), the mixture was refluxed for 3 hours and concentrated in vacuo to afford the crude product. This crude product was partitioned between ether and 1N hydrochloric acid, and washed with ether. The water phase was basified with saturated aqueous sodium hydrogen carbonate. The product was extracted with dichloromethane. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure carefully to avoid evaporating the product. To the resulting solution was added 4N hydrochloric acid in ethyl acetate. The solution was concentrated in vacuo to afford 2-methyl-[1,4]oxazepane hydrochloride as pale yellow oil (964 mg, 90%). The mixture was refluxed for 5 hours the mixture was refluxed for 3 hours concentrated in vacuo to afford the crude product This crude product was partitioned between ether and 1N hydrochloric acid washed with ether The product was extracted with dichloromethane The organic layer was dried over sodium sulfate the solvent was removed under reduced pressure carefully to avoid evaporating the product To the resulting solution was added 4N hydrochloric acid in ethyl acetate The solution was concentrated in vacuo