1-(5-bromo-2-fluorophenyl)propan-1-one

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

実験手順: A solution of 7.50 g (32.5 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanone (Example 4A) in 1-methyl-2-pyrrolidone (NMP; 100 ml) was treated with 3.25 g (3.16 ml, 64.9 mmol) hydrazine hydrate and stirred at reflux temperature for 16 h. Upon cooling, the mixture was poured into a mixture of ice and water. The precipitate was collected by filtration and washed thoroughly with water to yield 4.56 g (62% of th.) of the title compound as a beige-coloured solid. at reflux temperature for 16 h Upon cooling The precipitate was collected by filtration washed thoroughly with water

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

実験手順: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 3A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A solution of 7.50 g (32.5 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanone (Example 6A) in 1-methyl-2-pyrrolidinone (NMP; 100 ml) was treated with 3.25 g (3.16 ml, 64.9 mmol) hydrazine hydrate and stirred at reflux temperature for 16 h. Upon cooling, the mixture was poured into a mixture of ice and water. The precipitate was collected by filtration and washed thoroughly with water to yield 4.56 g (62% of th.) of the title compound as a beige-coloured solid. at reflux temperature for 16 h Upon cooling The precipitate was collected by filtration washed thoroughly with water

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

実験手順: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 5A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A solution of 7.50 g (32.5 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanone (Example 4A) in 1-methyl-2-pyrrolidone (NMP; 100 ml) was treated with 3.25 g (3.16 ml, 64.9 mmol) hydrazine hydrate and stirred at reflux temperature for 16 h. Upon cooling, the mixture was poured into a mixture of ice and water. The precipitate was collected by filtration and washed thoroughly with water to yield 4.56 g (62% of th.) of the title compound as a beige-coloured solid. at reflux temperature for 16 h Upon cooling The precipitate was collected by filtration washed thoroughly with water

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

実験手順: A solution of 7.50 g (32.5 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanone (Example 4A) in 1-methyl-2-pyrrolidone (NMP; 100 ml) was treated with 3.25 g (3.16 ml, 64.9 mmol) hydrazine hydrate and stirred at reflux temperature for 16 h. Upon cooling, the mixture was poured into a mixture of ice and water. The precipitate was collected by filtration and washed thoroughly with water to yield 4.56 g (62% of th.) of the title compound as a beige-coloured solid. at reflux temperature for 16 h Upon cooling The precipitate was collected by filtration washed thoroughly with water

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

実験手順: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 3A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A solution of 7.50 g (32.5 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanone (Example 6A) in 1-methyl-2-pyrrolidinone (NMP; 100 ml) was treated with 3.25 g (3.16 ml, 64.9 mmol) hydrazine hydrate and stirred at reflux temperature for 16 h. Upon cooling, the mixture was poured into a mixture of ice and water. The precipitate was collected by filtration and washed thoroughly with water to yield 4.56 g (62% of th.) of the title compound as a beige-coloured solid. at reflux temperature for 16 h Upon cooling The precipitate was collected by filtration washed thoroughly with water

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

実験手順: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 5A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

反応条件: temp:72.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-(5-bromo-2-fluorophenyl)propan-1-one (10 g, 43 mmol), anhydrous hydrazine (53 mL) was added and heated at reflux (70-75° C.) for 2 days. Excess hydrazine was distilled out under vacuum from the reaction mixture. To this was added xylene (60 mL) and the mixture heated to 145-150° C. for 3 days. Xylene was concentrated completely under vacuum to give a crude product, which was purified by column chromatography using 8% ethyl acetate/pet-ether as eluents to afford 5-bromo-3-ethyl-1H-indazole (4 g, 40%) as a solid. 1H NMR (CDCl3): δ 9.6-10.0 (br, 1H), 7.9 (s, 1H), 7.5 (d, 1H), 7.3 (d, 1H), 3.0 (q, 2H), 1.4 (t, 3H). heated Excess hydrazine was distilled out under vacuum from the reaction mixture To this was added xylene (60 mL) the mixture heated to 145-150° C. for 3 days Xylene was concentrated completely under vacuum to give a crude product, which was purified by column chromatography

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

実験手順: To 1-(5-bromo-2-fluorophenyl)propan-1-ol (12.1 g, 64.8 mmol) in CH2Cl2 (100 mL) was added pyridinium dichromate (73.2 g, 194 mmol) and powdered molecular sieves. The mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered through a pad of diatomaceous earth and washed with diethyl ether. The combined ether and CH2Cl2 layers were collected and concentrated under vacuum to afford 1-(5-bromo-2-fluorophenyl)propan-1-one (12.6 g, 98%) as a syrup. 1H NMR (CDCl3): δ 7.9-8.0 (m, 1H), 7.5-7.6 (m, 1H), 7.0 (t, 1H), 3.0-3.1 (m, 2H), 1.2 (t, 3H). The reaction mixture was filtered through a pad of diatomaceous earth washed with diethyl ether The combined ether and CH2Cl2 layers were collected concentrated under vacuum

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

実験手順: A solution of 7.50 g (32.5 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanone (Example 15A) in 1-methyl-2-pyrrolidinone (NMP; 100 ml) was treated with 3.25 g (3.16 ml, 64.9 mmol) hydrazine hydrate and stirred at reflux temperature for 16 h. Upon cooling, the mixture was poured into a mixture of ice and water. The precipitate was collected by filtration and washed thoroughly with water to yield 4.56 g (62% of th.) of the title compound as a beige-coloured solid. at reflux temperature for 16 h Upon cooling The precipitate was collected by filtration washed thoroughly with water