tert-butyl N-(4-chlorobut-2-ynyl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:

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: A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (1.51 g), tert-butyl (4-chlorobut-2-yn-1-yl)carbamate (2.60 g), cesium carbonate (4.80 g) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 2 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→33:67) to give the title compound (2.61 g) as an orange oil. the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was separated purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→33:67)

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

実験手順: A mixture of 4-chloro-5H-pyrrolo[3,2-d]pyrimidine (1.51 g), tert-butyl (4-chlorobut-2-yn-1-yl)carbamate (2.60 g), cesium carbonate (4.80 g) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 2 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→33:67) to give the title compound (2.61 g) as an orange oil. the mixture was extracted with ethyl acetate The organic layer washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was separated purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→33:67)

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

実験手順: Ex-8d) 12.1 g 1-t-Butyloxycarbonylamino-4-chloro-2-butyne is refluxed for 16 h with a mixture of 8 g diethyl acetamidomalonate and sodiumethoxide prepared from 900 mg of sodium in 100 mL of absolute ethanol. Ethanol is then removed under vacuum and the residual mass is partitioned between water and ethylacetate/ether (1:1). The organic layer is treated with 0.5N NaOH and 0.5N HCl and washed with water. It is then dried over Na2SO4, filtered and concentrated. The product is crystallized from ethylacetate/petroleum ether to give ˜7 g of Ethyl-2-acetylamino-6-t-butyloxycarbonylamino-2-ethoxycarbonyl-4-hexynoate. Ethanol is then removed under vacuum the residual mass is partitioned between water and ethylacetate/ether (1:1) The organic layer is treated with 0.5N NaOH and 0.5N HCl washed with water It is then dried over Na2SO4 filtered concentrated The product is crystallized from ethylacetate/petroleum ether

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

実験手順: Ex-8c) 14.1 g of 1-Amino-4-chloro-2-butyne hydrochloride was taken up in 70 mL of dioxane and :35 mL water. 4 g NaOH was added and the reaction mixture was stirred for 30 minutes followed by the addition of 21.8 g di-t-butylcarbonate at 20° C. The reaction mixture was stirred at 20° C. to 25° C. for 8 h and then the lower organic layer was separated. The upper aqueous layer was extracted with 100 mL of dichloromethane. Organic layers were combined and washed with 50% aqueous NaHCO3, dried over anhydrous MgSO4, treated with Darco, filtered over celite and concentrated to give a brown oil. This oil was chromatographed to give 9 g of 1-t-Butyloxycarbonylamino-4-chloro-2-butyne as a white solid. The reaction mixture was stirred at 20° C. to 25° C. for 8 h the lower organic layer was separated The upper aqueous layer was extracted with 100 mL of dichloromethane washed with 50% aqueous NaHCO3 dried over anhydrous MgSO4 treated with Darco filtered over celite and concentrated to give a brown oil This oil was chromatographed