4-fluoro-N-methylbenzenesulfonamide

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Following the general procedure for EXAMPLE 49 and making non-critical variations (-)-2-(isochroman-1-yl)ethanol (LXXIX, 0.394 g) and 4-(homopiperazin-1-yl)benzamide (IV; 0.601 g prepared by the method of EXAMPLE 47, Step 1 from 4-fluorobenzamide, III, and homopiperazine, II) are combined to give the title compound, mp 163.75-165°; MS (m/z) 379; [α]D -41° (c, 0.975, DMF); IR (mineral oil) 1609, 1043, 1662, 1167 and 1216 cm-1.

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-fluoro-N-methylbenzenesulfonamide (189 mg, 0.999 mmol) and piperazine (430 mg, 4.99 mmol) were combined and the reaction mixture was stirred at 120° C. for 2 h. It was diluted with water (5 mL) and stirred until a fine suspension resulted. The precipitate was filtered, washed with water (5×3 mL) and dried in vacuum to afford N-methyl-4-(piperazin-1-yl)benzenesulfonamide (222 mg, 0.869 mmol, 87% yield) as a white solid. ESI-MS: m/z 256 (M+H)+. stirred until a fine suspension resulted The precipitate was filtered washed with water (5×3 mL) dried in vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2.53 g (0.01 mol) of ethyl 4-chloro-1,3-dimethyl-1H pyrazolo[3,4-b]pyridine-5-carboxylate, 1.89 g (0.01 mol) of N-methyl-4-fluorobenzenesulfonamide, 6.91 g (0.05 mol) of anhydrous K2CO3, 0.143 g of 18-crown-6 and 70 ml of anhydrous 1-methyl-2-pyrrolidinone was stirred and heated at 100° C. for 17 hours. The solvent was removed under vacuum and water added to the residue. The mixture was extracted with CH2Cl2, and the extract washed with H2O, brine and dried (Na2SO4). The solution was filtered through a pad of hydrous magnesium silicate and the filtrate concentrated to dryness under vacuum to give 4.98 g of an oil. This oil was chromatographed on a silica gel column with ethyl acetate-hexane(2:3) as solvent to give 3.15 g of solid, mp 107-109° C. The solvent was removed under vacuum and water added to the residue The mixture was extracted with CH2Cl2 the extract washed with H2O, brine dried (Na2SO4) The solution was filtered through a pad of hydrous magnesium silicate the filtrate concentrated to dryness under vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2.53 g (0.01 mol) of ethyl 4-chloro-1,3-dimethyl-1H pyrazolo[3,4-b]pyridine-5-carboxylate, 1.89 g (0.01 mol) of N-methyl-4-fluorobenzenesulfonamide, 6.91 g (0.05 mol) of anhydrous K2CO3, 0.143 g of 18-crown-6 and 70 ml of anhydrous 1-methyl-2-pyrrolidinone was stirred and heated at 100° C. for 17 hours. The solvent was removed under vacuum and water added to the residue. The mixture was extracted with CH2Cl2, and the extract washed with H2O, brine and dried (Na2SO4). The solution was filtered through a pad of hydrous magnesium silicate and the filtrate concentrated to dryness under vacuum to give 4.98 g of an oil. This oil was chromatographed on a silica gel column with ethyl acetate-hexane(2:3) as solvent to give 3.15 g of solid, mp 107-109° C. The solvent was removed under vacuum and water added to the residue The mixture was extracted with CH2Cl2 the extract washed with H2O, brine dried (Na2SO4) The solution was filtered through a pad of hydrous magnesium silicate the filtrate concentrated to dryness under vacuum

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

Procedure: A mixture of 125 ml of methylamine (0.25 molar) in tetrahydrofuran and 13.9 ml (0.10 mol) of triethylamine was chilled in an ice bath. To this chilled solution was added dropwise 19.4 g (0.10 mol) of 4-fluorobenzenesulfonyl chloride in 150 ml of CH2Cl2 was added and the mixture refluxed for 2 hours and then stirred overnight at room temperature. The mixture was with CH2Cl2, washed with H2O, 2N citric acid, brine and dried (Na2SO4). The solution was filtered through a pad of hydrous magnesium silicate and the filtrate concentrated to dryness under vacuum to give 18.0 g of white solid, mp 67-70° C. was chilled in an ice bath was added the mixture refluxed for 2 hours washed with H2O, 2N citric acid, brine dried (Na2SO4) The solution was filtered through a pad of hydrous magnesium silicate the filtrate concentrated to dryness under vacuum

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

Procedure: Following the general procedure for EXAMPLE 49 and making non-critical variations (-)-2-(isochroman-1-yl)ethanol (LXXIX, 0.394 g) and 4-(homopiperazin-1-yl)benzamide (IV; 0.601 g prepared by the method of EXAMPLE 47, Step 1 from 4-fluorobenzamide, III, and homopiperazine, II) are combined to give the title compound, mp 163.75-165°; MS (m/z) 379; [α]D -41° (c, 0.975, DMF); IR (mineral oil) 1609, 1043, 1662, 1167 and 1216 cm-1.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(4-pyridyl)piperazine (0.86 g), N-methyl-4-fluorobenzenesulphonamide (1.00 g) and potassium carbonate (2.00 g) in N-methylpyrrolidone was stirred at 100° C. for 24 hours and then evaporated. The residue was partitioned between dichloromethane and 2N hydrochloric acid. The acid layer was washed with dichloromethane, filtered and made basic with sodium bicarbonate solution. The mixture was extracted several times with chloroform, and the combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was crystallised from ethanol/ethyl acetate to give the title compound (0.12 g), m.p. 204°-206° C. Found: C,57.55; H,6.13; N,16.62. C16H20N4O2S requires: C,57.81; H,6.06; N,16.85%. evaporated The residue was partitioned between dichloromethane and 2N hydrochloric acid The acid layer was washed with dichloromethane filtered The mixture was extracted several times with chloroform the combined extracts were washed with water dried over magnesium sulphate evaporated The residue was crystallised from ethanol/ethyl acetate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(4-pyridyl)piperazine (0.86 g), N-methyl-4-fluorobenzenesulphonamide (1.00 g) and potassium carbonate (2.00 g) in N-methylpyrrolidone was stirred at 100° C. for 24 hours and then evaporated. The residue was partitioned between dichloromethane and 2N hydrochloric acid. The acid layer was washed with dichloromethane, filtered and made basic with sodium bicarbonate solution. The mixture was extracted several times with chloroform, and the combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was crystallised from ethanol/ethyl acetate to give the title compound (0.12 g), m.p. 204°-206° C. Found: C,57.55; H,6.13; N,16.62. C16H20N4O2S requires: C,57.81; H,6.06; N,16.85%. evaporated The residue was partitioned between dichloromethane and 2N hydrochloric acid The acid layer was washed with dichloromethane filtered The mixture was extracted several times with chloroform the combined extracts were washed with water dried over magnesium sulphate evaporated The residue was crystallised from ethanol/ethyl acetate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(4-pyridyl)piperazine (0.86 g), N-methyl-4-fluorobenzenesulphonamide (1.00 g) and potassium carbonate (2.00 g) in N-methylpyrrolidone was stirred at 100° C. for 24 hours and then evaporated. The residue was partitioned between dichloromethane and 2N hydrochloric acid. The acid layer was washed with dichloromethane, filtered and made basic with sodium bicarbonate solution. The mixture was extracted several times with chloroform, and the combined extracts were washed with water, dried over magnesium sulphate and evaporated. The residue was crystallised from ethanol/ethyl acetate to give the title compound (0.12 g), m.p. 204°-206° C. Found: C,57.55; H,6.13; N,16.62. C16H20N4O2S requires: C,57.81; H,6.06; N,16.85%. evaporated The residue was partitioned between dichloromethane and 2N hydrochloric acid The acid layer was washed with dichloromethane filtered The mixture was extracted several times with chloroform the combined extracts were washed with water dried over magnesium sulphate evaporated The residue was crystallised from ethanol/ethyl acetate

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-fluoro-N-methylbenzenesulfonamide (189 mg, 0.999 mmol) and piperazine (430 mg, 4.99 mmol) were combined and the reaction mixture was stirred at 120° C. for 2 h. It was diluted with water (5 mL) and stirred until a fine suspension resulted. The precipitate was filtered, washed with water (5×3 mL) and dried in vacuum to afford N-methyl-4-(piperazin-1-yl)benzenesulfonamide (222 mg, 0.869 mmol, 87% yield) as a white solid. ESI-MS: m/z 256 (M+H)+. stirred until a fine suspension resulted The precipitate was filtered washed with water (5×3 mL) dried in vacuum