2-氰基-N-[(2,4-二氟苯基)甲基]乙酰胺

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4,4,4-Trifluoro-1-[1-(3-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-butane-1,3-dione (143 mg, 0.41 mmol) and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (86 mg, 0.41 mmol) were suspended in 1.5 mL anhydrous benzene. To the above reaction mixture was added 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU (31 mg, 0.21 mmol). The mixture was heated at 90° C. under nitrogen atmosphere for overnight. After this period of time, the mixture was evaporated in vacuo and the resulting residue was purified by column chromatography on silica gel (35% EtOAC/Hexane) to give 1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-6-[1-(3-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-1,2-dihydro-pyridine-3-carbonitrile as a yellow solid (78 mg, 36% yield). 1H-NMR (400 MHz, CDCl3): δ 5.42 (s, 2H), 6.61 (s, 1H), 6.82 (m, 1H), 6.89 (m, 1H), 7.12 (m, 1H), 7.58 (dd, 1H, J=4.80, J=8.08), 7.73 (s, 1H), 8.28 (dd, 1H, J=1.77, J=8.08), 8.32 (s, 1H), 8.72 (dd, 1H, J=1.77, J=4.80). After this period of time the mixture was evaporated in vacuo the resulting residue was purified by column chromatography on silica gel (35% EtOAC/Hexane)

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

实验步骤: To a solution of 1-(4-bromo-furan-2-yl)-4,4-difluoro-hexane-1,3-dione (220 mg, 0.75 mmol), and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (300 mg, 1.4 mmol) in benzene (4 mL) was added 1,8-diaza-bicycle-[5.4.0]-undec-7-ene (60 μL, 0.4 mmol). The red reaction mixture was then heated to reflux. After 3 hours, heating was discontinued and the reaction was allowed to cool to ambient temperature. After stirring at ambient temperature for 16 hours the reaction mixture was diluted with CH2Cl2 and purified by adsorbing the material onto silica gel, loading the resulting solid onto the column and eluting with a gradient from 0% to 30% ethyl acetate/hexane to afford 6-(4-bromo-furan-2-yl)-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-propyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (188 mg, 54% yield) as a yellow oil. 1H-NMR (400 MHz, CDCl3): δ 7.62 (1H, s), 7.1-7.03 (1H, m), 6.86-6.78 (2H, m), 6.76 (1H, s), 6.64 (1H, s), 5.46 (2H, s), 2.31 (2H, t of q, JH-H=7.6 Hz, JH-F=16.9 Hz), 1.11 (3H, t, J=7.6 Hz). The red reaction mixture was then heated to reflux heating purified eluting with a gradient from 0% to 30% ethyl acetate/hexane

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

实验步骤: To a solution of 1-(4-bromo-furan-2-yl)-4,4-difluoro-hexane-1,3-dione (220 mg, 0.75 mmol), and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (300 mg, 1.4 mmol) in benzene (4 mL) was added 1,8-diaza-bicycle-[5.4.0]-undec-7-ene (60 μL, 0.4 mmol). The red reaction mixture was then heated to reflux. After 3 hours, heating was discontinued and the reaction was allowed to cool to ambient temperature. After stirring at ambient temperature for 16 hours the reaction mixture was diluted with CH2Cl2 and purified by adsorbing the material onto silica gel, loading the resulting solid onto the column and eluting with a gradient from 0% to 30% ethyl acetate/hexane to afford 6-(4-bromo-furan-2-yl)-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-propyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (188 mg, 54% yield) as a yellow oil. 1H-NMR (400 MHz, CDCl3): δ 7.62 (1H, s), 7.1-7.03 (1H, m), 6.86-6.78 (2H, m), 6.76 (1H, s), 6.64 (1H, s), 5.46 (2H, s), 2.31 (2H, t of q, JH-H=7.6 Hz, JH-F=16.9 Hz), 1.11 (3H, t, J=7.6 Hz). The red reaction mixture was then heated to reflux heating purified eluting with a gradient from 0% to 30% ethyl acetate/hexane

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4,4,4-Trifluoro-1-[1-(3-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-butane-1,3-dione (143 mg, 0.41 mmol) and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (86 mg, 0.41 mmol) were suspended in 1.5 mL anhydrous benzene. To the above reaction mixture was added 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU (31 mg, 0.21 mmol). The mixture was heated at 90° C. under nitrogen atmosphere for overnight. After this period of time, the mixture was evaporated in vacuo and the resulting residue was purified by column chromatography on silica gel (35% EtOAC/Hexane) to give 1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-6-[1-(3-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-1,2-dihydro-pyridine-3-carbonitrile as a yellow solid (78 mg, 36% yield). 1H-NMR (400 MHz, CDCl3): δ 5.42 (s, 2H), 6.61 (s, 1H), 6.82 (m, 1H), 6.89 (m, 1H), 7.12 (m, 1H), 7.58 (dd, 1H, J=4.80, J=8.08), 7.73 (s, 1H), 8.28 (dd, 1H, J=1.77, J=8.08), 8.32 (s, 1H), 8.72 (dd, 1H, J=1.77, J=4.80). After this period of time the mixture was evaporated in vacuo the resulting residue was purified by column chromatography on silica gel (35% EtOAC/Hexane)

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

实验步骤: To a solution of 1-(4-bromo-furan-2-yl)-4,4-difluoro-hexane-1,3-dione (220 mg, 0.75 mmol), and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (300 mg, 1.4 mmol) in benzene (4 mL) was added 1,8-diaza-bicycle-[5.4.0]-undec-7-ene (60 μL, 0.4 mmol). The red reaction mixture was then heated to reflux. After 3 hours, heating was discontinued and the reaction was allowed to cool to ambient temperature. After stirring at ambient temperature for 16 hours the reaction mixture was diluted with CH2Cl2 and purified by adsorbing the material onto silica gel, loading the resulting solid onto the column and eluting with a gradient from 0% to 30% ethyl acetate/hexane to afford 6-(4-bromo-furan-2-yl)-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-propyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (188 mg, 54% yield) as a yellow oil. 1H-NMR (400 MHz, CDCl3): δ 7.62 (1H, s), 7.1-7.03 (1H, m), 6.86-6.78 (2H, m), 6.76 (1H, s), 6.64 (1H, s), 5.46 (2H, s), 2.31 (2H, t of q, JH-H=7.6 Hz, JH-F=16.9 Hz), 1.11 (3H, t, J=7.6 Hz). The red reaction mixture was then heated to reflux heating purified eluting with a gradient from 0% to 30% ethyl acetate/hexane

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4,4,4-Trifluoro-1-[1-(3-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-butane-1,3-dione (143 mg, 0.41 mmol) and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (86 mg, 0.41 mmol) were suspended in 1.5 mL anhydrous benzene. To the above reaction mixture was added 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU (31 mg, 0.21 mmol). The mixture was heated at 90° C. under nitrogen atmosphere for overnight. After this period of time, the mixture was evaporated in vacuo and the resulting residue was purified by column chromatography on silica gel (35% EtOAC/Hexane) to give 1-(2,4-difluoro-benzyl)-2-oxo-4-trifluoromethyl-6-[1-(3-trifluoromethyl-pyridin-2-yl)-1H-pyrazol-4-yl]-1,2-dihydro-pyridine-3-carbonitrile as a yellow solid (78 mg, 36% yield). 1H-NMR (400 MHz, CDCl3): δ 5.42 (s, 2H), 6.61 (s, 1H), 6.82 (m, 1H), 6.89 (m, 1H), 7.12 (m, 1H), 7.58 (dd, 1H, J=4.80, J=8.08), 7.73 (s, 1H), 8.28 (dd, 1H, J=1.77, J=8.08), 8.32 (s, 1H), 8.72 (dd, 1H, J=1.77, J=4.80). After this period of time the mixture was evaporated in vacuo the resulting residue was purified by column chromatography on silica gel (35% EtOAC/Hexane)

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

实验步骤: To a solution of 1-(4-bromo-furan-2-yl)-4,4-difluoro-hexane-1,3-dione (220 mg, 0.75 mmol), and 2-cyano-N-(2,4-difluoro-benzyl)-acetamide (300 mg, 1.4 mmol) in benzene (4 mL) was added 1,8-diaza-bicycle-[5.4.0]-undec-7-ene (60 μL, 0.4 mmol). The red reaction mixture was then heated to reflux. After 3 hours, heating was discontinued and the reaction was allowed to cool to ambient temperature. After stirring at ambient temperature for 16 hours the reaction mixture was diluted with CH2Cl2 and purified by adsorbing the material onto silica gel, loading the resulting solid onto the column and eluting with a gradient from 0% to 30% ethyl acetate/hexane to afford 6-(4-bromo-furan-2-yl)-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-propyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (188 mg, 54% yield) as a yellow oil. 1H-NMR (400 MHz, CDCl3): δ 7.62 (1H, s), 7.1-7.03 (1H, m), 6.86-6.78 (2H, m), 6.76 (1H, s), 6.64 (1H, s), 5.46 (2H, s), 2.31 (2H, t of q, JH-H=7.6 Hz, JH-F=16.9 Hz), 1.11 (3H, t, J=7.6 Hz). The red reaction mixture was then heated to reflux heating purified eluting with a gradient from 0% to 30% ethyl acetate/hexane