3-oxo-2-phenylbutanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of α-acetylphenylacetonitrile (1.0 g, 6.3 mmol) in acetonitrile (25 mL) was added 4-chlorobenzyl bromide (1.3 g, 6.3 mmol) and cesium carbonate (8.2 g, 25 mmol). After stirring at room temperature for 2 h, the reaction mixture was poured into ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated to dryness, and the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.5-6.9 (m, 9H), 3.56 (d, 1H), 3.37 (d, 1H), 2.22 (s, 3H). LC-MS: m/e 306 (M+Na)+ (3.0 min). The organic layer was separated washed with brine dried over magnesium sulfate filtered concentrated to dryness the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of α-acetylphenylacetonitrile (1.0 g, 6.3 mmol) in acetonitrile (25 mL) was added 4-chlorobenzyl bromide (1.3 g, 6.3 mmol) and cesium carbonate (8.2 g, 25 mmol). After stirring at room temperature for 2 h, the reaction mixture was poured into ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated to dryness, and the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.5-6.9 (m, 9H), 3.56 (d, 1H), 3.37 (d, 1H), 2.22 (s, 3H). LC-MS: m/e 306 (M+Na)+ (3.0 min). The organic layer was separated washed with brine dried over magnesium sulfate filtered concentrated to dryness the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-iodoisonicotinic acid (180 mg, 0.72 mmol), potassium carbonate (199 mg, 1.44 mmol), 1-(5-fluoro-2-methylphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-amine (202 mg, 0.72 mmol, synthesized in the same manner as Intermediate F, using commercially available 2-phenylacetoacetonitrile as the nitrile source), and copper (II) acetate (6.5 mg, 0.04 mmol) in DMF (1 mL) was heated (150° C.) in a sealed tube for 16 h. The mixture was cooled to rt, filtered through a silica gel plug using ethyl acetate as eluent, concentrated to dryness, and subjected to HPLC purification using a gradient elution from 30% to 90% acetonitrile in water to afford 29.1 mg (10%) of the desired product. 1H NMR (300 MHz, CD3CN) δ 9.39 (br s, 1H), 7.93 (s, 1H), 7.86-7.90 (m, 2H), 7.05-7.45 (m, 8H), 2.38 (s, 3H), 2.15 (s, 3H); ES-MS m/z 403.1 (MH+), HPLC RT (min) 2.40. synthesized in the same manner as Intermediate F The mixture was cooled to rt filtered through a silica gel plug concentrated to dryness subjected to HPLC purification a gradient elution from 30% to 90% acetonitrile in water

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of α-acetylphenylacetonitrile (1.0 g, 6.3 mmol) in acetonitrile (25 mL) was added 4-chlorobenzyl bromide (1.3 g, 6.3 mmol) and cesium carbonate (8.2 g, 25 mmol). After stirring at room temperature for 2 h, the reaction mixture was poured into ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated to dryness, and the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.5-6.9 (m, 9H), 3.56 (d, 1H), 3.37 (d, 1H), 2.22 (s, 3H). LC-MS: m/e 306 (M+Na)+ (3.0 min). The organic layer was separated washed with brine dried over magnesium sulfate filtered concentrated to dryness the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: α-Acetylphenylacetonitrile (10 g) was dissolved in methanol (100 mL), and hydrazinoethanol (5.3 g) was added, and the mixture was heated under reflux for 4 hrs. After the completion of the reaction, the solvent was evaporated. The obtained residue was subjected to silica gel column chromatography, and the fraction eluted with chloroform:methanol=40:1 was concentrated to give 5-amino-1-(2-hydroxyethyl)-3-methyl-4-phenylpyrazole (11.4 g) as white crystals. the mixture was heated under reflux for 4 hrs After the completion of the reaction the solvent was evaporated the fraction eluted with chloroform methanol=40:1 was concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (α-acetylphenylacetonitrile (1.0 g, 6.3 mmol) in acetonitrile (25 mL) was added 4-chlorobenzyl bromide (1.3 g, 6.3 mmol) and cesium carbonate (8.2 g, 25 mmol). After stirring at room temperature for 2 h, the reaction mixture was poured into ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated to dryness, and the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.5-6.9 (m, 9H), 3.56 (d, 1H), 3.37 (d, 1H), 2.22 (s, 3H). LC-MS: m/e 306 (M+Na)+ (3.0 min). The organic layer was separated washed with brine dried over magnesium sulfate filtered concentrated to dryness the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of α-acetylphenylacetonitrile (1.0 g, 6.3 mmol) in acetonitrile (25 mL) was added 4-chlorobenzyl bromide (1.3 g, 6.3 mmol) and cesium carbonate (8.2 g, 25 mmol). After stirring at room temperature for 2 h, the reaction mixture was poured into ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated to dryness, and the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.5-6.9 (m, 9H), 3.56 (d, 1H), 3.37 (d, 1H), 2.22 (s, 3H). LC-MS: m/e 306 (M+Na)+ (3.0 min). The organic layer was separated washed with brine dried over magnesium sulfate filtered concentrated to dryness the residue was purified on a silica gel column eluting with 1 to 5% ethyl acetate in hexane