1-bromopentan-2-one

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

Procedure: To a mixture of sodium hydride (60% dispersion in mineral oil, 0.8 g) in DMF (50 ml) was added ethyl 3-amino-pyrazol-4-carboxylate (2.0 g) and the reaction mixture was stirred at room temperature for 15 minutes. After addition of 1-bromo-2-pentanone (4.0 g), the mixture was stirred at room temperature for 13 hours. The reaction mixture was concentrated to dryness, and the residue was dissolved in ethyl acetate-water. The organic layer was washed with water, dried and concentrated to dryness. The resulting yellow syrup was purified by column chromatography on silica gel to give pale yellow prisms (1.4 g, 45%). the mixture was stirred at room temperature for 13 hours The reaction mixture was concentrated to dryness the residue was dissolved in ethyl acetate-water The organic layer was washed with water dried concentrated to dryness The resulting yellow syrup was purified by column chromatography on silica gel

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

Procedure: To a mixture of sodium hydride (60% dispersion in mineral oil, 0.8 g) in DMF (50 ml) was added ethyl 3-amino-pyrazol-4-carboxylate (2.0 g) and the reaction mixture was stirred at room temperature for 15 minutes. After addition of 1-bromo-2-pentanone (4.0 g), the mixture was stirred at room temperature for 13 hours. The reaction mixture was concentrated to dryness, and the residue was dissolved in ethyl acetate-water. The organic layer was washed with water, dried and concentrated to dryness. The resulting yellow syrup was purified by column chromatography on silica gel to give pale yellow prisms (1.4 g, 45%). the mixture was stirred at room temperature for 13 hours The reaction mixture was concentrated to dryness the residue was dissolved in ethyl acetate-water The organic layer was washed with water dried concentrated to dryness The resulting yellow syrup was purified by column chromatography on silica gel

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

Procedure: 10-bromo-2-hydroxy-4H-pyrido3,2,1-jk]carbazole-4-one (250 mg) obtained in Example 59 was suspended in dimethyl sulfoxide (10 ml), and potassium carbonate (210 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 1-bromo-2-pentanone (170 mg) was added to the mixture. The mixture was stirred at room temperature for 3 hours, and the reaction mixture was poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol) to obtain the title compound (130 mg, 41%). The mixture was stirred at room temperature for 3 hours extracted with ethyl acetate The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol)

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

Procedure: 10-bromo-2-hydroxy-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4-one (250 mg) obtained in Example 49 was suspended in dimethyl sulfoxide (10 ml), and potassium carbonate (210 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 1-bromo-2-pentanone (188 mg) was added to the mixture. The mixture was stirred at room temperature for 12 hours, and the reaction mixture was poured into ice water (500 ml), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol) to obtain the title compound (150 mg, 48%). The mixture was stirred at room temperature for 12 hours extracted with ethyl acetate The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol)

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

Procedure: To a mixture of sodium hydride (60% dispersion in mineral oil, 0.8 g) in DMF (50 ml) was added ethyl 3-amino-pyrazol-4-carboxylate (2.0 g) and the reaction mixture was stirred at room temperature for 15 minutes. After addition of 1-bromo-2-pentanone (4.0 g), the mixture was stirred at room temperature for 13 hours. The reaction mixture was concentrated to dryness, and the residue was dissolved in ethyl acetate-water. The organic layer was washed with water, dried and concentrated to dryness. The resulting yellow syrup was purified by column chromatography on silica gel to give pale yellow prisms (1.4 g, 45%). the mixture was stirred at room temperature for 13 hours The reaction mixture was concentrated to dryness the residue was dissolved in ethyl acetate-water The organic layer was washed with water dried concentrated to dryness The resulting yellow syrup was purified by column chromatography on silica gel

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

Procedure: Prepared from N,N-dicyclopropyl-6-ethyl-1-methyl-4-thioureido-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 2B) and 1-bromopentan-2-one using the same procedure as reported for 2.

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

Procedure: Prepared from N,N-dicyclopropyl-6-ethyl-1-methyl-4-thioureido-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 2B) and 1-bromopentan-2-one using the same procedure as reported for 2.

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

Procedure: 10-bromo-2-hydroxy-4H-pyrido[3,2,1-jk]carbazole-4-one (250 mg) obtained in Example 59 was suspended in dimethyl sulfoxide (10 ml), and potassium carbonate (210 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 1-bromo-2-pentanone (170 mg) was added to the mixture. The mixture was stirred at room temperature for 3 hours, and the reaction mixture was poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol) to obtain the title compound (130 mg, 41%). The mixture was stirred at room temperature for 3 hours extracted with ethyl acetate The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol)

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

Procedure: 10-bromo-2-hydroxy-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4-one (250 mg) obtained in Example 49 was suspended in dimethyl sulfoxide (10 ml), and potassium carbonate (210 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 1-bromo-2-pentanone (188 mg) was added to the mixture. The mixture was stirred at room temperature for 12 hours, and the reaction mixture was poured into ice water (500 ml), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol) to obtain the title compound (150 mg, 48%). The mixture was stirred at room temperature for 12 hours extracted with ethyl acetate The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol)

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

Procedure: Prepared from N,N-dicyclopropyl-6-ethyl-1-methyl-4-thioureido-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 2B) and 1-bromopentan-2-one using the same procedure as reported for 2.

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

Procedure: 10-bromo-2-hydroxy-4H-pyrido3,2,1-jk]carbazole-4-one (250 mg) obtained in Example 59 was suspended in dimethyl sulfoxide (10 ml), and potassium carbonate (210 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 1-bromo-2-pentanone (170 mg) was added to the mixture. The mixture was stirred at room temperature for 3 hours, and the reaction mixture was poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol) to obtain the title compound (130 mg, 41%). The mixture was stirred at room temperature for 3 hours extracted with ethyl acetate The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol)

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

Procedure: 10-bromo-2-hydroxy-5-methyl-4H-pyrido[3,2,1-jk]carbazole-4-one (250 mg) obtained in Example 49 was suspended in dimethyl sulfoxide (10 ml), and potassium carbonate (210 mg) was added to the suspension. The mixture was stirred at room temperature for 30 minutes and 1-bromo-2-pentanone (188 mg) was added to the mixture. The mixture was stirred at room temperature for 12 hours, and the reaction mixture was poured into ice water (500 ml), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol) to obtain the title compound (150 mg, 48%). The mixture was stirred at room temperature for 12 hours extracted with ethyl acetate The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel flash column chromatography (eluent: methylene chloride containing 2% methanol)