1-amino-3-methylbutan-2-one;hydrochloride

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

Procedure: 4.0 g of isobutyrylmethylamine hydrochloride, 6.1 g of sodium bicarbonate and 5.1 g of 4-fluorobenzoyl chloride are treated in the same manner as described in Preparation 1-(4). 5.8 g of N-(4-fluorobenzoyl)isobutyrylmethylamine are thereby obtained. Yield: 89.2%. as described in Preparation 1-(4)

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

Procedure: 4.5 g of isobutyrylmethylamine hydrochloride, 11 g of sodium bicarbonate and 4.81 g of benzoyl chloride are treated in the same manner as described in Preparation 1-(4). 6.07 g of N-benzoylisobutyrylmethylamine are thereby obtained. Yield: 90.5%. as described in Preparation 1-(4)

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

Procedure: 4.5 g of isobutyrylmethylamine hydrochloride, 11 g of sodium bicarbonate and 4.81 g of benzoyl chloride are treated in the same manner as described in Preparation 1-(4). 6.07 g of N-benzoylisobutyrylmethylamine are thereby obtained. Yield: 90.5%. as described in Preparation 1-(4)

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

Procedure: 4.5 g of 4-chlorobenzoyl chloride are added dropwise to a mixture of 4 g of isobutyrylmethylamine hydrochloride, 9.8 g of sodium bicarbonate, 200 ml of ethyl acetate and 100 ml of water at 5° C. to 10° C. under stirring. The mixture is further stirred at room temperature for 3 hours. The ethyl acetate layer is collected, and said layer is washed with water, dried and then condensed under reduced pressure to remove solvent. 6.1 g of N-(4-chlorobenzoyl)isobutyrylmethylamine are obtained. Yield: 87.5%. The mixture is further stirred at room temperature for 3 hours The ethyl acetate layer is collected is washed with water dried condensed under reduced pressure to remove solvent

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

Procedure: 4.5 g of 4-chlorobenzoyl chloride are added dropwise to a mixture of 4 g of isobutyrylmethylamine hydrochloride, 9.8 g of sodium bicarbonate, 200 ml of ethyl acetate and 100 ml of water at 5° C. to 10° C. under stirring. The mixture is further stirred at room temperature for 3 hours. The ethyl acetate layer is collected, and said layer is washed with water, dried and then condensed under reduced pressure to remove solvent. 6.1 g of N-(4-chlorobenzoyl)isobutyrylmethylamine are obtained. Yield: 87.5%. The mixture is further stirred at room temperature for 3 hours The ethyl acetate layer is collected is washed with water dried condensed under reduced pressure to remove solvent

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

Procedure: The same operation as in Example (lb) was performed using 1-amino-3-methylbutan-2-one hydrochloride obtained in Example (35c) (about 17.6 mmol) and ethyl imino(methylthio)acetate tetrafluoroborate obtained according to a method known in the literature (J. Med. Chem., 38, 1995, 2196-2201) (about 22 mmol), to obtain 1.83 g of the title compound as a yellow solid (57%). obtained

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

Procedure: The same operation as in Example (lb) was performed using 1-amino-3-methylbutan-2-one hydrochloride obtained in Example (35c) (about 17.6 mmol) and ethyl imino(methylthio)acetate tetrafluoroborate obtained according to a method known in the literature (J. Med. Chem., 38, 1995, 2196-2201) (about 22 mmol), to obtain 1.83 g of the title compound as a yellow solid (57%). obtained

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution containing 0.32 g of 4-amino-2-methyl-3-butanone hydrochloride, 0.33 g of ethyl acetoacetate and 0.28 g of sodium acetate in 2 ml of 75% acetic acid was heated at 100° C. for 1.5 h. The mixture was poured into 10 ml of water and extracted three times with 10 ml of diethyl ether. Combined extracts were washed three times with 10 ml of saturated sodium hydrogen carbonate and with 10 ml of brine then dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was purified by flash chromatography on silica gel using dichloromethane for the elution to give 0.15 g of ethyl 4-isopropyl-2-methyl-1H-pyrrole-3-carboxylate. Recrystallisation from isohexane gave analytically pure material of melting point 67-68.5° C.; mass spectrum (EI) m/z 195 [M]+. extracted three times with 10 ml of diethyl ether Combined extracts were washed three times with 10 ml of saturated sodium hydrogen carbonate with 10 ml of brine then dried over anhydrous magnesium sulphate filtered evaporated The residue was purified by flash chromatography on silica gel for the elution

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

Procedure: The same operation as in Example (1b) was performed using 1-amino-3-methylbutan-2-one hydrochloride obtained in Example (35c) (about 17.6 mmol) and ethyl imino(methylthio)acetate tetrafluoroborate obtained according to a method known in the literature (J. Med. Chem., 38, 1995, 2196-2201) (about 22 mmol), to obtain 1.83 g of the title compound as a yellow solid (57%). obtained

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

Procedure: 4.0 g of isobutyrylmethylamine hydrochloride, 6.1 g of sodium bicarbonate and 5.1 g of 4-fluorobenzoyl chloride are treated in the same manner as described in Preparation 1-(4). 5.8 g of N-(4-fluorobenzoyl)isobutyrylmethylamine are thereby obtained. Yield: 89.2%. as described in Preparation 1-(4)

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

Procedure: 4.5 g of isobutyrylmethylamine hydrochloride, 11 g of sodium bicarbonate and 4.81 g of benzoyl chloride are treated in the same manner as described in Preparation 1-(4). 6.07 g of N-benzoylisobutyrylmethylamine are thereby obtained. Yield: 90.5%. as described in Preparation 1-(4)

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

Procedure: 4.5 g of 4-chlorobenzoyl chloride are added dropwise to a mixture of 4 g of isobutyrylmethylamine hydrochloride, 9.8 g of sodium bicarbonate, 200 ml of ethyl acetate and 100 ml of water at 5° C. to 10° C. under stirring. The mixture is further stirred at room temperature for 3 hours. The ethyl acetate layer is collected, and said layer is washed with water, dried and then condensed under reduced pressure to remove solvent. 6.1 g of N-(4-chlorobenzoyl)isobutyrylmethylamine are obtained. Yield: 87.5%. The mixture is further stirred at room temperature for 3 hours The ethyl acetate layer is collected is washed with water dried condensed under reduced pressure to remove solvent