3-氨基丁酸-2-腈

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

实验步骤: 100 mg (1.026 mmol) cyclopentane-1,3-dione, 150 mg (1.026 mmol) 1H-indazole-5-carbaldehyde and piperidine (0.1 ml) in ethanol (8 ml) were heated to reflux for 4 h. The mixture was then evaporated to dryness, the remaining solid was dissolved in acetic acid (8 ml), and 84 mg (1.026 mmol) 3-aminobut-2-enenitrile were added. The solution was heated to reflux for 2 h. After cooling, the mixture was evaporated to dryness again, and the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient) to yield 40 mg (13% of th.) of the title compound. to reflux for 4 h The mixture was then evaporated to dryness the remaining solid was dissolved in acetic acid (8 ml) The solution was heated to reflux for 2 h After cooling the mixture was evaporated to dryness again the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient)

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

实验步骤: 91 mg (0.936 mmol) cyclopentane-1,3-dione, 150 mg (0.936 mmol) 3-methyl-1H-indazole-5-carbaldehyde (Example 1A) and piperidine (0.1 ml) in ethanol (8 ml) were heated to reflux for 1.5 h and then left standing without stirring at room temperature overnight. The mixture was then evaporated to dryness, the remaining solid was dissolved in acetic acid (8 ml), and 77 mg (0.936 mmol) 3-aminobut-2-enenitrile were added. The solution was heated to reflux for 2 h. After cooling, the mixture was evaporated to dryness again, and the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient) to yield 34 mg (12% of th.) of the title compound. to reflux for 1.5 h left standing The mixture was then evaporated to dryness the remaining solid was dissolved in acetic acid (8 ml) The solution was heated to reflux for 2 h After cooling the mixture was evaporated to dryness again the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient)

反应条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 250 mL round bottom flask was charged with 3-aminobut-2-enenitrile (10.00 g, 122 mmol), 2,2,6-trimethyl-4H-1,3-dioxin-4-one (32.4 mL, 244 mmol), and a magnetic stir bar. The flask was equipped with a reflux condenser and a CaCl2 tube and the reaction mixture was heated at 130° C. for 1 h. The reaction was allowed to cool room temperature and was diluted with EtOAc (100 mL). The solid that formed was collected, washed with EtOAc (20 mL), and dried to give 2,6-dimethyl-4-oxo-1,4-dihydropyridine-3-carbonitrile (3.5 g, 23.62 mmol, 19.4% yield) as a beige soild. 1H NMR (400 MHz, DMSO-d6) δ 11.94 (br. s., 1H), 6.04 (s, 1H), 2.41 (s, 3H), 2.21 (s, 3H). MS(ES) [M+H]+ 148.9. The flask was equipped with a reflux condenser and a CaCl2 tube to cool room temperature The solid that formed was collected washed with EtOAc (20 mL) dried

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

实验步骤: The crude product obtained in Example 8A and 29.6 mg (0.361 mmol) 3-aminobut-2-enenitrile in acetic acid (4 ml) were heated to 110° C. for 1 h. After cooling, the reaction mixture was directly purified by preparative RP-HPLC (acetonitrile/water+0.05% TFA gradient) yielding 30 mg (46% of th.) of the title compound. After cooling the reaction mixture was directly purified by preparative RP-HPLC (acetonitrile/water+0.05% TFA gradient)

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

实验步骤: 3,4-Dichlorophenyl hydrazine HCl (50.0 g.) was reacted with 3-amino-2-butene nitrile (18.31 g.) as described in Example XLIII to give 18.7 g. product, mp 110°-112°. to give 18.7 g

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

实验步骤: 5-chloro-2-methylphenylhydrazine HCl (80.32 g.) was reacted with 3-amino-2-butene nitrile (32.5 g.) as described in Example XLIII to give 60.5 g. product, mp 86°-87°. to give 60.5 g

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

实验步骤: 5-chloro-2-methylphenylhydrazine HCl (80.32 g.) was reacted with 3-amino-2-butene nitrile (32.5 g.) as described in Example XLIII to give 60.5 g. product, mp 86°-87°. to give 60.5 g

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

实验步骤: 3-Trifluoromethylphenyl hydrazine (Tetrahedron, 1960, 69) (25.0 g.) was reacted with 3-amino-2-butene nitrile (12.7 g.) as described in Example XLIII to give 36.1 g. product as HCl salt, mp 222°-226°. to give 36.1 g

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

实验步骤: 3-Trifluoromethylphenyl hydrazine (Tetrahedron, 1960, 69) (25.0 g.) was reacted with 3-amino-2-butene nitrile (12.7 g.) as described in Example XLIII to give 36.1 g. product as HCl salt, mp 222°-226°. to give 36.1 g

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

实验步骤: 66 mg (0.19 mmol) of cyclobutylmethyl 2-[(2-methyl-4-oxo-4H-chromen-8-yl)methylene]-3-oxobutanoate are dissolved with 16 mg (0.19 mmol) of 3-aminobut-2-enenitrile in 3 ml of ethanol and heated under reflux under argon for 24 h. The suspension is allowed to cool and filtered with suction, and the remaining solid is washed with methanol. 45 mg (57% of theory) of the title compound are obtained as a white solid. heated under reflux under argon for 24 h to cool filtered with suction the remaining solid is washed with methanol

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

实验步骤: 100 mg (1.026 mmol) cyclopentane-1,3-dione, 150 mg (1.026 mmol) 1H-indazole-5-carbaldehyde and piperidine (0.1 ml) in ethanol (8 ml) were heated to reflux for 4 h. The mixture was then evaporated to dryness, the remaining solid was dissolved in acetic acid (8 ml), and 84 mg (1.026 mmol) 3-aminobut-2-enenitrile were added. The solution was heated to reflux for 2 h. After cooling, the mixture was evaporated to dryness again, and the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient) to yield 40 mg (13% of th.) of the title compound. to reflux for 4 h The mixture was then evaporated to dryness the remaining solid was dissolved in acetic acid (8 ml) The solution was heated to reflux for 2 h After cooling the mixture was evaporated to dryness again the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient)

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

实验步骤: 100 mg (1.026 mmol) cyclopentane-1,3-dione, 150 mg (1.026 mmol) 1H-indazole-5-carbaldehyde and piperidine (0.1 ml) in ethanol (8 ml) were heated to reflux for 4 h. The mixture was then evaporated to dryness, the remaining solid was dissolved in acetic acid (8 ml), and 84 mg (1.026 mmol) 3-aminobut-2-enenitrile were added. The solution was heated to reflux for 2 h. After cooling, the mixture was evaporated to dryness again, and the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient) to yield 40 mg (13% of th.) of the title compound. to reflux for 4 h The mixture was then evaporated to dryness the remaining solid was dissolved in acetic acid (8 ml) The solution was heated to reflux for 2 h After cooling the mixture was evaporated to dryness again the remaining solid was purified by preparative RP-HPLC (acetonitrile/water gradient)