(2-fluorophenyl)hydrazine

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 stirred solution, under nitrogen of 35.2 g of 2-fluorophenylhydrazine in 250 ml of dry pyridine, cooled in an ice bath, was added, dropwise, 36.7 ml of 2-fluorobenzoyl chloride. The reaction mixture was stirred at ambient temperature for 21 hours. Upon dilution of the reaction mixture with water a precipitate was formed. Attempts to separate the precipitate by filtration, washing with pyridine, resulted in the formation of an oil. That portion of oil which did not pass into the filtrate was dissolved in dichloromethane and concentrated in vacuo. Upon standing, the filtrate separated into aqueous and organic phases Treatment of the organic phase with toluene resulted in the formation of a precipitate. Recrystallization of the combined product from toluene yielded 49.2 g of 2-fluorobenzoic acid, 2-(2-fluorophenyl)hydrazide. was added to separate the precipitate by filtration washing with pyridine resulted in the formation of an oil concentrated in vacuo the filtrate separated into aqueous and organic phases Treatment of the organic phase with toluene resulted in the formation of a precipitate Recrystallization of the combined product from toluene

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

Procedure: Ethyl 4-oxo-1,4-dihydroquinoline-3-carboxylate (3.8 g, 17 mmol) was dissolved in phosphorus oxychloride (25 mL, 0.26 mol, 15 equiv) and stirred at ambient temperature for 14 hours. The mixture was concentrated in vacuo and the residue was concentrated from toluene (3×25 mL). The resulting residue was dissolved in 1,2-dimethoxyethane (60 mL) and degassed N,N-dimethylformamide (10 mL) and treated with 2-fluorophenylhydrazine (4.4 g, 35 mmol, 2 equiv) and potassium carbonate (12 g, 87 mmol, 5 equiv). The mixture was placed into a preheated oil bath at 80° C. for 14 hours. The mixture was cooled to ambient temperature, diluted with water (100 mL) and ethyl acetate (100 mL) and filtered. The solid was collected and dried in vacuo, providing the titled compound as a yellow solid. The mixture was concentrated in vacuo the residue was concentrated from toluene (3×25 mL) The resulting residue was dissolved in 1,2-dimethoxyethane (60 mL) degassed N,N-dimethylformamide (10 mL) The mixture was placed into a preheated oil bath at 80° C. for 14 hours The mixture was cooled to ambient temperature filtered The solid was collected dried in vacuo

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

Procedure: Ethyl 1-[(2-fluoro-4-iodophenyl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylate (1.4 g, 3.1 mmol) was dissovled in phosphorus oxychloride (6.0 mL, 64 mmol, 21 equiv) and stirred for 2.5 hours at ambient temperature. The mixture was diluted with toluene (10 mL) and concentrated in vacuo. The residue was dissolved in dioxane (17 mL), treated with 2-fluorophenylhydrazine (0.87 g, 6.8 mmol, 2.2 equiv) and potassium carbonate (1.3 g, 9.4 mmol, 3 equiv) and stirred at ambient temperature for 5 minutes. The mixture was placed into a preheated oil bath at 80° C. for 1 hour, cooled to ambient temperature and diluted with chloroform (150 mL). The organic mixture was washed once with water (50 mL) and brine (50 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with a chloroform:methanol (95:5) solution (30 mL). The solid was filtered and dried in vacuo, providing the titled compound. concentrated in vacuo The residue was dissolved in dioxane (17 mL) stirred at ambient temperature for 5 minutes The mixture was placed into a preheated oil bath at 80° C. for 1 hour cooled to ambient temperature The organic mixture was washed once with water (50 mL) and brine (50 mL) dried with sodium sulfate filtered concentrated in vacuo The residue was triturated with a chloroform:methanol (95:5) solution (30 mL) The solid was filtered dried in vacuo

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

Procedure: 2-Fluorophenyl hydrazine (1.26 g, 9.99 mmol) and ethyl 3-(2-fluorophenyl)-3-oxopropanoate (2.10 g, 9.99 mmol, 1 equiv) were combined in acetic acid (20 mL) and placed into an oil bath preheated at 120° C. for 3 hours. The mixture was cooled of ambient temperature and concentrated in vacuo. The residue was concentrated from toluene (3×50 mL), providing the titled compound. placed into an oil bath concentrated in vacuo The residue was concentrated from toluene (3×50 mL)

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

Procedure: The title compound was prepared following procedure for 23a using 2-fluorophenyl hydrazine instead of phenyl hydrazine. 1H-NMR (DMSO-d6) δ (ppm): 7.37 (3H, m), 7.52 (2H, m), 7.81 (2H, m), 8.74 (1H, s). m/z 298.3 (MH+).

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

Procedure: The title compound was prepared following procedure for 23a using 2-fluorophenyl hydrazine instead of phenyl hydrazine. 1H-NMR (DMSO-d6) δ (ppm): 7.37 (3H, m), 7.52 (2H, m), 7.81 (2H, m), 8.74 (1H, s). m/z 298.3 (MH+).

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

Procedure: 2-Chloro-6-[2-fluorophenylhydrazino]-9-cyclopentylpurine is prepared from 2,6-dichloro-9-cyclopentylpurine, 2-fluorophenylhydrazine, and triethylamine essentially as described above in Example 1, Scheme A, step b.

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

Procedure: 2-Chloro-6-[2-fluorophenylhydrazino]-9-cyclopentylpurine is prepared from 2,6-dichloro-9-cyclopentylpurine, 2-fluorophenylhydrazine, and triethylamine essentially as described above in Example 1, Scheme A, step b.

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

Procedure: To a stirred solution, under nitrogen of 35.2 g of 2-fluorophenylhydrazine in 250 ml of dry pyridine, cooled in an ice bath, was added, dropwise, 36.7 ml of 2-fluorobenzoyl chloride. The reaction mixture was stirred at ambient temperature for 21 hours. Upon dilution of the reaction mixture with water a precipitate was formed. Attempts to separate the precipitate by filtration, washing with pyridine, resulted in the formation of an oil. That portion of oil which did not pass into the filtrate was dissolved in dichloromethane and concentrated in vacuo. Upon standing, the filtrate separated into aqueous and organic phases. Treatment of the organic phase with toluene resulted in the formation of a precipitate. Recrystallization of the combined product from toluene yielded 49.2 g of 2-fluorobenzoic acid, 2-(2-fluorophenyl)hydrazide. was added to separate the precipitate by filtration washing with pyridine resulted in the formation of an oil concentrated in vacuo the filtrate separated into aqueous and organic phases Treatment of the organic phase with toluene resulted in the formation of a precipitate Recrystallization of the combined product from toluene