chloro(dimethylphosphoryl)methane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 316.3 g of chloromethyl-dimethylphosphine oxide, 547 ml of benzylamine and 500 ml of ethanol is refluxed for 18 hours. After cooling to 20° to 25° C., the turbid suspension is filtered; the clear filtrate is then concentrated by evaporation, and to the residue are added 500 ml of 10% sodium chloride solution. The aqueous solution is extracted 4 times with 500 ml of methylene chloride each time; and the combined organic phases are subsequently dried over sodium sulfate and concentrated by evaporation. Vacuum distillation of the oily crude product yields 311.0 g (63% of theory) of N-benzyl-P,P-dimethyl-aminomethylphosphine oxide in the form of yellowish oil, b.p. 150° C./0.2 mb. After cooling to 20° to 25° C. the turbid suspension is filtered the clear filtrate is then concentrated by evaporation to the residue are added 500 ml of 10% sodium chloride solution The aqueous solution is extracted 4 times with 500 ml of methylene chloride each time and the combined organic phases are subsequently dried over sodium sulfate concentrated by evaporation Vacuum distillation of the oily crude product

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 4.3 g of 1-phenyl-3-(1-piperazinyl)-1H-indazole (prepared as in Example 2), 2.3 g of potassium carbonate, and 2.3 g of chloromethyldimethylphosphine oxide in 75 ml of dimethylformamide was heated at 90°, under nitrogen, for 16 hrs. Additional chloromethyldimethylphosphine oxide (0.6 g) was added, and the reaction mixture heated at 90° C. for 24 hrs. The reaction mixture was poured into water and the aqueous solution extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated to an oil. Flash chromatography of the oil on silica gel, eluting with dichloromethane/methanol (10%) followed by concentration of the appropriate fractions and trituration with diethyl ether gave 2.5 g (45%) of 3-[4-(dimethylphosphinylmethyl)-1-piperazinyl)]-1-phenyl-1H-indazole. was heated at 90°, under nitrogen, for 16 hrs the aqueous solution extracted with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate concentrated to an oil Flash chromatography of the oil on silica gel, eluting with dichloromethane/methanol (10%)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of 4-Piperazin-1-ylmethyl-benzoic acid (4c) and chloro-(dimethyl-phosphinoyl)-methane (5a) in ethanol was added potassium carbonate. The resulting reaction mixture was refluxed, then cooled to room temperature, diluted with brine, acidified to pH˜4, and extracted with EtOAc until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated on rotary evaporator. The desired product was purified by silica gel flash chromatography. The resulting reaction mixture was refluxed extracted with EtOAc until the aqueous layer The combined organics were dried over MgSO4 concentrated on rotary evaporator The desired product was purified by silica gel flash chromatography

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

実験手順: To a solution of 4-Piperazin-1-ylmethyl-benzoic acid (4c) and chloro-(dimethyl-phosphinoyl)-methane (5a) in ethanol was added potassium carbonate. The resulting reaction mixture was refluxed, then cooled to room temperature, diluted with brine, acidified to pH˜4, and extracted with EtOAc until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated on rotary evaporator. The desired product was purified by silica gel flash chromatography. The resulting reaction mixture was refluxed extracted with EtOAc until the aqueous layer The combined organics were dried over MgSO4 concentrated on rotary evaporator The desired product was purified by silica gel flash chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring mixture of 9.0 g of potassium carbonate in 100 ml of dimethylformamide was added 8.0 g of 4-(2,3,4,5,6-pentafluorophenoxy)piperidine and 9.5 g of dimethylphosphinylmethyl chloride. After stirring at 80° C. for 30 hours, the reaction mixture was cooled, poured into water, and extracted with ethyl acetate. The organic layer was washed with water followed by a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, evaporation afforded a residue which was purified by means of high pressure liquid chromatography (silica gel; elution with 5% methanol/dichloromethane). The desired fractions were evaporated to yield a solid which was sublimed to afford 2.37 g (22.1%) of 1-[(dimethylphosphinyl)methyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine, m.p. 120°-123° C. the reaction mixture was cooled extracted with ethyl acetate The organic layer was washed with water dried over anhydrous magnesium sulfate After filtering evaporation afforded a residue which was purified by means of high pressure liquid chromatography (silica gel; elution with 5% methanol/dichloromethane) The desired fractions were evaporated to yield a solid which

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

実験手順: To a solution of 4-Piperazin-1-ylmethyl-benzoic acid (4c) and chloro-(dimethyl-phosphinoyl)-methane (5a) in ethanol was added potassium carbonate. The resulting reaction mixture was refluxed, then cooled to room temperature, diluted with brine, acidified to pH˜4, and extracted with EtOAc until the aqueous layer showed little or no evidence of product by HPLC. The combined organics were dried over MgSO4 and concentrated on rotary evaporator. The desired product was purified by silica gel flash chromatography. The resulting reaction mixture was refluxed extracted with EtOAc until the aqueous layer The combined organics were dried over MgSO4 concentrated on rotary evaporator The desired product was purified by silica gel flash chromatography