3-(2-bromophenyl)-3-oxopropanenitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(2-bromophenyl)-3-oxopropanenitrile (15 g, 66.94 mmol) in DMSO (267 mL) were added sodium salt of methanesulfonic acid (13.6 g, 138.89 mmol), copper iodide (6.3 g, 33.47 mmol), L-proline (3.8 g, 33.47 mmol) and sodium hydroxide (1.3 g, 33.47 mmol) at 25° C. The reaction mixture was stirred for 1 h at 60° C. Water was added to the reaction mixture at 25° C. and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 0-45% EtOAc in hexane to give 3-(2-(methylsulfonyl)phenyl)-3-oxopropanenitrile: 1H NMR (400 MHz, CHLOROFORM-d): δ 3.183 (S, 3H), 4.041 (s, 2H), 7.468 (dd, 1H, J=1.2 Hz, J=7.6 Hz), 7.699-7.798 (m, 2H), 8.084 (dd, 1H, J=1.2 Hz, J=7.6 Hz); LC-MS (ESI) m/z 224.0 [M+H]+. extracted with EtOAc The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography on silica gel using 0-45% EtOAc in hexane

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

実験手順: To a solution of 3-(2-bromo-phenyl)-3-oxo-propionitrile (1.8 g, 8.03 mmol) in absolute EtOH (25 mL) was added hydrazine hydrate (2.3 mL, 48.2 mmol). The reaction mixture was refluxed for 23 hours, then cooled and purified directly on silica gel with 0-10% MeOH in CH2Cl2 as eluent to provide 1.33 g (70% yield) of 5-amino-3-(2-bromophenyl)pyrazole as a sticky oil. 1H-NMR (d6-DMSO) δ: 11.7 (broad m, 1H, tautomers), 7.20-7.70 (broad m, 4H), 5.76 (broad m, 1H), 5.03 (broad s, 1H), 4.60 (broad s, 1H); HPLC/MS m/z: 238.0, 240.0 [MH]+. The reaction mixture was refluxed for 23 hours cooled purified directly on silica gel with 0-10% MeOH in CH2Cl2 as eluent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of NaH (60% dispersion, 1.14 g, 28.4 mmol) in dry THF (50 mL) under N2 was added CH3CN followed by 2-bromo-benzoic acid methyl ester (2 mL, 14.2 mmol). The reaction mixture was refluxed for 1.5 hour, then cooled to 0° C., quenched with water (1 mL), and concentrated in vacuo. The residue was diluted with water and the aqueous layer was extracted with hexane (2×), then acidified to pH 3-4 with 1N aqueous HCl. The milky aqueous layer was extracted with CHCl3 (3×), the combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification on silica gel with 0-35% EtOAc in hexane as eluent provided 1.89 g (59 % yield) of 3-(2-bromo-phenyl)-3-oxo-propionitrile as a yellow oil. 1H-NMR (d6-DMSO) δ: 11.8 (broad m, 1H, tautomers), 7.73 (broad s, 1H), 7.42 (m, 3H), 4.99 (s, 0.3H, tautomer), 4.64 (s, 0.6H, tautomer); HPLC/MS m/z: 223.9, 225.9 [MH]+. The reaction mixture was refluxed for 1.5 hour quenched with water (1 mL) concentrated in vacuo The residue was diluted with water the aqueous layer was extracted with hexane (2×) The milky aqueous layer was extracted with CHCl3 (3×) the combined organic layers were dried over sodium sulfate filtered concentrated Purification on silica gel with 0-35% EtOAc in hexane as eluent

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(2-bromophenyl)-3-oxopropanenitrile (15 g, 66.94 mmol) in DMSO (267 mL) were added sodium salt of methanesulfonic acid (13.6 g, 138.89 mmol), copper iodide (6.3 g, 33.47 mmol), L-proline (3.8 g, 33.47 mmol) and sodium hydroxide (1.3 g, 33.47 mmol) at 25° C. The reaction mixture was stirred for 1 h at 60° C. Water was added to the reaction mixture at 25° C. and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 0-45% EtOAc in hexane to give 3-(2-(methylsulfonyl)phenyl)-3-oxopropanenitrile: 1H NMR (400 MHz, CHLOROFORM-d): δ 3.183 (S, 3H), 4.041 (s, 2H), 7.468 (dd, 1H, J=1.2 Hz, J=7.6 Hz), 7.699-7.798 (m, 2H), 8.084 (dd, 1H, J=1.2 Hz, J=7.6 Hz); LC-MS (ESI) m/z 224.0 [M+H]+. extracted with EtOAc The organic layer was dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography on silica gel using 0-45% EtOAc in hexane