1-(2-aminophenyl)-3-methylbutan-1-one

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: At reflux, a solution of 29.5 g (0.25 mol) of anthranilonitrile in 150 ml of tetrahydrofuran is added dropwise to a suspension comprising 18.2 g (0.75 mmol) of magnesium, 375 ml of a 2 M solution of isobutylmagnesium bromide in tetrahydrofuran and 15 ml of diethyl ether. After 5 h of heating under reflux, 100 ml of water are, at 0° C., added to the reaction mixture, and the pH is adjusted to 6 using hydrochloric acid. The organic phase is washed with water and dried over magnesium sulphate. Concentration under reduced pressure and purification on silica gel (mobile phase: petroleum ether/acetonitrile 95:5) gives 11.0 g (25% of theory) of 1-(2-aminophenyl)-3-methylbutan-1-one of logP (pH 2.3)=2.89. At reflux After 5 h of heating under reflux are, at 0° C. added to the reaction mixture The organic phase is washed with water dried over magnesium sulphate Concentration under reduced pressure and purification on silica gel (mobile phase: petroleum ether/acetonitrile 95:5)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At room temperature, 355.0 mg (2.0 mmol) of 1-(2-aminophenyl)-3-methylbutan-1-one are added to a solution comprising 388.5 mg (2.2 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride and 0.45 ml (3.2 mmol) of triethylamine in 20 ml of tetrahydrofuran. The reaction mixture is stirred at 60° C. for 1.5 h, filtered through silica gel and concentrated. Column chromatography (cyclohexane/ethyl acetate: 3/1) gives 577.7 mg (1.8 mmol, 88% of theory) of N-[2-(3-methylbutyryl)phenyl-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide of logP (pH=2.3)=3.42. filtered through silica gel concentrated

Conditions: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution comprising 8.0 g (0.045 mol) of 1-(2-aminophenyl)-3-methylbutan-1-one (X-1), 6.8 g (0.135 mol) of hydrazine hydrate and 7.6 g (0.135 mol) of potassium hydroxide in 90 ml of triethylene glycol is heated at 210° C. for 6 h. For work-up, water and ethyl acetate are added at room temperature. The organic phase is again washed with water, dried over magnesium sulphate and concentrated under reduced pressure. Purification by column chromatography (cyclohexane/ethyl acetate 3:1) gives 5.3 g (71.5% of theory) of [2-(3-methylbutyl)-phenyl]amine. The organic phase is again washed with water dried over magnesium sulphate concentrated under reduced pressure Purification by column chromatography (cyclohexane/ethyl acetate 3:1)