甲基3-溴-2-氧代丙酸酯

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

实验步骤: In 20 ml of chlorobenzene were dissolved 1.1 g (5.0 mmol) of 4-phenyl-1,2,3-thiadiazole-5-carbothioamide and 0.92 g (5.0 mmol) of methyl bromopyruvate. The solution thus obtained was stirred for 3 hours with heating under reflux. After the reaction was completed, the reaction mixture was cooled to room temperature, a saturated aqueous solution of sodium hydrogen carbonate was added thereto, and the objective product was extracted with ethyl acetate. The solvent was distilled off from the extract solution under a reduced pressure, and the residue was purified by silica gel column chromatography using 3:1 mixture of n-hexane and ethyl acetate. Thus, 0.74 g of the objective compound was obtained. The solution thus obtained with heating under reflux the objective product was extracted with ethyl acetate The solvent was distilled off from the extract solution under a reduced pressure the residue was purified by silica gel column chromatography 3:1 mixture of n-hexane and ethyl acetate

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-chloropyrazin-2-amine (52 g, 401 mmol) in acetonitrile (750 mL) under N2 was added sodium bicarbonate (67.4 g, 803 mmol), and then methyl bromopyruvate (97 mL, 803 mmol). The mixture was then heated to 80° C. for 4 hours and then cooled to r.t. The reaction was then diluted water (2200 mL) and stirred for 30 minutes. The resulting solids were filtered, azeotroped with EtOAc (2 L), and dried overnight at 40° C. under vacuum and nitrogen sweep to give the title compound (60 g). LRMS (ESI) calc (M+H)+=212.0. found 212.0 cooled to r.t The resulting solids were filtered azeotroped with EtOAc (2 L) dried overnight at 40° C. under vacuum and nitrogen sweep

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

实验步骤: In 20 ml of chlorobenzene were dissolved 1.1 g (5.0 mmol) of 4-phenyl-1,2,3-thiadiazole-5-carbothioamide and 0.92 g (5.0 mmol) of methyl bromopyruvate. The solution thus obtained was stirred for 3 hours with heating under reflux. After the reaction was completed, the reaction mixture was cooled to room temperature, a saturated aqueous solution of sodium hydrogen carbonate was added thereto, and the objective product was extracted with ethyl acetate. The solvent was distilled off from the extract solution under a reduced pressure, and the residue was purified by silica gel column chromatography using 3:1 mixture of n-hexane and ethyl acetate. Thus, 0.74 g of the objective compound was obtained. The solution thus obtained with heating under reflux the objective product was extracted with ethyl acetate The solvent was distilled off from the extract solution under a reduced pressure the residue was purified by silica gel column chromatography 3:1 mixture of n-hexane and ethyl acetate

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A reaction mixture of 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)pyridazin-3-amine (11.0 g, 32.2 mmol), methyl 3-bromo-2-oxopropanoate (11.67 g, 64.5 mmol), and NaHCO3 (10.84 g) in dioxane (150 mL) was heated at 80° C. for 4 hrs to provide a red reaction mixture. Solids were filtered off, rinsed with dioxane, and the combined filtrates were concentrated via rotary evaporation. The resulting residue was dissolved in EtOAc and washed with 0.1 N NaOH until the red color no longer persisted. The organic phase was then separated and concentrated to dryness. The resulting material was purified via MPLC (5:95, MeOH/EtOAc) to provide the title compound, 45I (4.0 g, 9.45 mmol, 30%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.88 (s, 3 H) 7.77 (dd, J=9.73, 1.64 Hz, 1 H) 7.85 (d, J=9.60 Hz, 1 H) 7.97-8.08 (m, 1 H) 8.53 (d, J=9.60 Hz, 1 H) 8.98 (d, J=1.01 Hz, 1 H) 9.02 (s, 1 H). ESI-MS:m/z 423.1 (M+H)+. to provide a red reaction mixture Solids were filtered off rinsed with dioxane the combined filtrates were concentrated via rotary evaporation The resulting residue was dissolved in EtOAc washed with 0.1 N NaOH until the red color The organic phase was then separated concentrated to dryness The resulting material was purified via MPLC (5:95, MeOH/EtOAc)

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

实验步骤: In 20 ml of chlorobenzene were dissolved 1.1 g (5.0 mmol) of 4-phenyl-1,2,3-thiadiazole-5-carbothioamide and 0.92 g (5.0 mmol) of methyl bromopyruvate. The solution thus obtained was stirred for 3 hours with heating under reflux. After the reaction was completed, the reaction mixture was cooled to room temperature, a saturated aqueous solution of sodium hydrogen carbonate was added thereto, and the objective product was extracted with ethyl acetate. The solvent was distilled off from the extract solution under a reduced pressure, and the residue was purified by silica gel column chromatography using 3:1 mixture of n-hexane and ethyl acetate. Thus, 0.74 g of the objective compound was obtained. The solution thus obtained with heating under reflux the objective product was extracted with ethyl acetate The solvent was distilled off from the extract solution under a reduced pressure the residue was purified by silica gel column chromatography 3:1 mixture of n-hexane and ethyl acetate

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-chloropyrazin-2-amine (52 g, 401 mmol) in acetonitrile (750 mL) under N2 was added sodium bicarbonate (67.4 g, 803 mmol), and then methyl bromopyruvate (97 mL, 803 mmol). The mixture was then heated to 80° C. for 4 hours and then cooled to r.t. The reaction was then diluted water (2200 mL) and stirred for 30 minutes. The resulting solids were filtered, azeotroped with EtOAc (2 L), and dried overnight at 40° C. under vacuum and nitrogen sweep to give the title compound (60 g). LRMS (ESI) calc (M+H)+=212.0. found 212.0 cooled to r.t The resulting solids were filtered azeotroped with EtOAc (2 L) dried overnight at 40° C. under vacuum and nitrogen sweep