3-(二甲基氨基亚甲基)-6-甲基吡喃-2,4-二酮

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(dimethylaminomethylene)-4-oxo-6-methyl-2-pyrone (85.0 g) and ammonium hydroxide (500 ml) is slowly heated to 70° C. with the condenser outlet open. The mixture is heated at 70°-80° C. for 3 hours, concentrated to a volume of about 100 ml and acidified with 3N HCl to pH 5. The product is filtered and washed with water and diethyl ether to give 38.6 g of the title compound. Physical characteristics are as follows: The mixture is heated at 70°-80° C. for 3 hours concentrated to a volume of about 100 ml The product is filtered washed with water and diethyl ether

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

实验步骤: N,N-dimethylformamide dimethyl acetal (150 ml) is added dropwise to a mixture of 4-hydroxy-6-methyl-2-pyrone (100 g) in dioxane (400 ml) at 0° C. over 20 minutes. The mixture is warmed to room temperature and stirred an additional 4 hours. The precipitated solid is filtered, washed with isopropanol and dried to give 85.0 g of the title compound. The filtrate is concentrated and isopropanol (300 ml) is added to the residue. This mixture is kept at 0° C. overnight to give an additional 18.8 g of the title compound. Physical characteristics are as follows: The precipitated solid is filtered washed with isopropanol dried

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

实验步骤: A solution of 3-dimethylaminomethylene-6-methyl-pyran-2,4-dione (preparation 1a, 10.00 g, 38.6 mmol based on 70% purity), isopropylamine (5.00 mL, 58.4 mmol) and sodium tert-butoxide (5.50 g, 57.2 mmol) in ethanol (20 mL) is heated for 18 h at 90° C. The reaction mixture is evaporated under reduced pressure, treated with water and extracted with dichloromethane. The aqueous layer is acidified with 4 N aqueous HCl and extracted with dichloromethane. The combined organic layer is washed with water, dried over Na2SO4 and evaporated under reduced pressure. Yield: 7.16 g; ESI mass spectrum: [M+H]+=196; r.t. HPLC: 0.71 min (Z002_006). The reaction mixture is evaporated under reduced pressure treated with water extracted with dichloromethane extracted with dichloromethane The combined organic layer is washed with water dried over Na2SO4 evaporated under reduced pressure r.t 0.71 min (Z002_006)

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-hydroxy-6-methyl-2-pyrone (11.50 g, 91.2 mmol) in toluene (30 mL) is added N,N-dimethylformamide dimethyl acetal (13.00 mL, 97.9 mmol). After stirring for 2 h at room temperature, the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times. Yield: 18.5 g; ESI mass spectrum: [M+H]+=182; r.t. HPLC: 0.72 min (Z002_007). the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times r.t 0.72 min (Z002_007)

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

实验步骤: A solution of 3-dimethylaminomethylene-6-methyl-pyran-2,4-dione (preparation 3a, 10.00 g, 38.6 mmol based on 70% purity), isopropylamine (5.00 mL, 58.4 mmol) and sodium tert-butoxide (5.50 g, 57.2 mmol) in ethanol (20 mL) is heated for 18 h at 90° C. The reaction mixture is evaporated under reduced pressure, treated with water and extracted with dichloromethane. The aqueous layer is acidified with 4 N aqueous HCl and extracted with dichloromethane. The combined organic layer is washed with water, dried over Na2SO4 and evaporated under reduced pressure. Yield: 7.16 g; ESI mass spectrum: [M+H]+=196; Retention time HPLC: 0.71 min (Z002_006). The reaction mixture is evaporated under reduced pressure treated with water extracted with dichloromethane extracted with dichloromethane The combined organic layer is washed with water dried over Na2SO4 evaporated under reduced pressure 0.71 min (Z002_006)

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-hydroxy-6-methyl-2-pyrone (11.50 g, 91.2 mmol) in toluene (30 mL) is added N,N-dimethylformamide dimethyl acetal (13.00 mL, 97.9 mmol). After stirring for 2 h at room temperature, the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times. Yield: 18.5 g; ESI mass spectrum: [M+H]+=182; Retention time HPLC: 0.72 min (Z002_007). the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times 0.72 min (Z002_007)

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-hydroxy-6-methyl-2-pyrone (11.50 g, 91.2 mmol) in toluene (30 mL) is added N,N-dimethylformamide dimethyl acetal (13.00 mL, 97.9 mmol). After stirring for 2 h at room temperature, the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times. Yield: 18.5 g; ESI mass spectrum: [M+H]+=182; Retention time HPLC: 0.72 min (Z002_007). the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times 0.72 min (Z002_007)

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

实验步骤: A solution of 3-dimethylaminomethylene-6-methyl-pyran-2,4-dione (preparation 1a, 2.00 g, 9.38 mmol based on 85% purity), 4-cyanobenzylamine hydrochloride (4.00 mL, 23.7 mmol) and sodium tert-butoxide (2.74 g, 28.5 mmol) in ethanol (11 mL) is heated for 48 h at 90° C. The reaction mixture is acidified with 4N aqueous HCl and extracted several times with dichloromethane. The combined organic layer is dried over Na2SO4, evaporated under reduced pressure and purified by preparative reversed-phase HPLC (Sunfire, gradient of methanol in water, 0.1% TFA, 60° C.). Yield: 0.94 g (37% of theory); ESI mass spectrum: [M+H]+=269; Retention time HPLC: 0.86 min (Z002—005). extracted several times with dichloromethane The combined organic layer is dried over Na2SO4 evaporated under reduced pressure purified by preparative reversed-phase HPLC (Sunfire, gradient of methanol in water, 0.1% TFA, 60° C.) 0.86 min (Z002—005)

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-hydroxy-6-methyl-2-pyrone (11.50 g, 91.2 mmol) in toluene (30 mL) is added N,N-dimethylformamide dimethyl acetal (13.00 mL, 97.9 mmol). After stirring for 2 h at room temperature, the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times. Yield: 18.5 g; ESI mass spectrum: [M+H]+=182; Retention time HPLC: 0.72 min (Z002—007). the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times 0.72 min (Z002—007)

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-hydroxy-6-methyl-2-pyrone (11.50 g, 91.2 mmol) in toluene (30 mL) is added N,N-dimethylformamide dimethyl acetal (13.00 mL, 97.9 mmol). After stirring for 2 h at room temperature, the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times. Yield: 18.5 g; ESI mass spectrum: [M+H]+=182; Retention time HPLC: 0.72 min (Z002—007). the reaction mixture is evaporated under reduced pressure and co-evaporated with toluene several times 0.72 min (Z002—007)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(dimethylaminomethylene)-4-oxo-6-methyl-2-pyrone (85.0 g) and ammonium hydroxide (500 ml) is slowly heated to 70° C. with the condenser outlet open. The mixture is heated at 70°-80° C. for 3 hours, concentrated to a volume of about 100 ml and acidified with 3N HCl to pH 5. The product is filtered and washed with water and diethyl ether to give 38.6 g of the title compound. Physical characteristics are as follows: The mixture is heated at 70°-80° C. for 3 hours concentrated to a volume of about 100 ml The product is filtered washed with water and diethyl ether

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

实验步骤: N,N-dimethylformamide dimethyl acetal (150 ml) is added dropwise to a mixture of 4-hydroxy-6-methyl-2-pyrone (100 g) in dioxane (400 ml) at 0° C. over 20 minutes. The mixture is warmed to room temperature and stirred an additional 4 hours. The precipitated solid is filtered, washed with isopropanol and dried to give 85.0 g of the title compound. The filtrate is concentrated and isopropanol (300 ml) is added to the residue. This mixture is kept at 0° C. overnight to give an additional 18.8 g of the title compound. Physical characteristics are as follows: The precipitated solid is filtered washed with isopropanol dried