1-(4-fluorophenyl)sulfonylpropan-2-one

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(4-Fluorophenylsulfonyl)propan-2-one (150 mg, 0.69 mmol), 3-methyl-1H-pyrazol-5-amine (67 mg, 0.69 mmol) and 3,4-dichlorobenzaldehyde (121 mg, 0.69 mmol) were dissolved in THF (5 mL), to which was added a catalytic amount of piperidine (3 drops). The reaction in a sealed tube was stirred at 70° C. for about 48 hrs. After cooling to rt., solvent was removed and crude product was purified by HPLC (acetonitrile-water, 5% to 95% gradient) to provide pure Step B product 7-(3,4-dichlorophenyl)-6-(4-fluorophenylsulfonyl)-2,5-dimethyl-4,7-dihydropyrazolo[1,5-a]pyrimidine as a solid. LC-MS found: (M+1)+=452.17. The two enantiomers were readily separated on Chiral PAK AS using 15% EtOH-MeOH in heptane. The reaction in a sealed tube After cooling to rt , solvent was removed crude product was purified by HPLC (acetonitrile-water, 5% to 95% gradient)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: NaOH (1.0M, 40.5 mL, 40.5 mmol) was added at 0° C. to a solution of 4-fluorothiophenol (5.20 g, 40.5 mmol) in methanol (100 mL) followed by addition of chloroacetone (3.87 mL, 48.6 mmol). The reaction was stirred at 0° C. for 5 minutes. Oxone (50 g, 81 mmol) was added all at once. The suspension was stirred at 0° C. and monitored by LC-MS until there was no sulfoxide (reaction intermediate) observed. The reaction was filtered and solid washed with diethyl ether. Most organic solvents were removed from the filtrate. The solution was extracted with diethyl ether three times. Combined organic phases were extracted with 5% NaOH aq. solution three times. Combined aqueous phases were acidified with 1.0N hydrochloric acid to precipitate product. Pure Step A product, 1-(4-fluorophenylsulfonyl)propan-2-one, was obtained after flash chromatography (silica gel, 3:7 ethyl acetate:hexanes) as a white solid. LC-MS found: (M+1)+=217.2. The suspension was stirred at 0° C. The reaction was filtered solid washed with diethyl ether Most organic solvents were removed from the filtrate The solution was extracted with diethyl ether three times Combined organic phases were extracted with 5% NaOH aq. solution three times to precipitate product