piperidine-1-sulfonamide

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: Piperidine (3.0 g) and sulfamide (5.93 g) in 1,4-dioxane (100 ml) were heated at reflux for 24 h. The solvent was evaporated under reduced pressure and the resulting solid suspended in CHCl3. The suspension was filtered and the filtrate concentrated in vacuo to afford the subtitle compound as a white solid. Yield: 3.85 g. at reflux for 24 h The solvent was evaporated under reduced pressure The suspension was filtered the filtrate concentrated in vacuo

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

Procedure: To a slurry of the piperidine sulfonamide from part F (6.3 g, 12.0 mmol) in methanol (25 mL) was added ammonium formate (2.2 g, 34.5 mmol). The system was purged with nitrogen for 10 minutes. The nitrogen stream was removed and palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added. The reaction was refluxed for forty five minutes, cooled, filtered through Celite under nitrogen, and concentrated in vacuo. The residue (4.5 g, 10 mmol) was dissolved in dry dimethylformamide (20 mL) and potassium carbonate (3.45 g, 325 mmol) and 2-chloro-5-ethylpyrimidine (1.82 mL, 15 mmol) were added. The reaction was stirred at eighty degrees Celsius for four hour and then concentrated in vacuo. The residue was taken up in ethyl acetate and filtered through Celite. The filtrate washed with water two times, saturated sodium chloride solution, dried over Na2SO4, filtered, and concentrated in vacuo. The product was recrystallized (methanol) to give the N-pyrimidinyl piperidine sulfonamide as a white solid (3.33 g, 60%). The system was purged with nitrogen for 10 minutes The nitrogen stream was removed palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added The reaction was refluxed for forty five minutes cooled filtered through Celite under nitrogen concentrated in vacuo concentrated in vacuo filtered through Celite The filtrate washed with water two times, saturated sodium chloride solution dried over Na2SO4 filtered concentrated in vacuo The product was recrystallized (methanol)

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

Procedure: To a slurry of the piperidine sulfonamide from part F (6.3 g, 12.0 mmol) in methanol (25 mL) was added ammonium formate (2.2 g, 34.5 mmol). The system was purged with nitrogen for 10 minutes. The nitrogen stream was removed and palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added. The reaction was refluxed for forty five minutes, cooled, filtered through Celite under nitrogen, and concentrated in vacuo. The residue (4.5 g, 10 mmol) was dissolved in dry dimethylformamide (20 mL) and potassium carbonate (4.14 g, 30 mmol) and 2-chloro-4-trifluoromethylpyrimidine (2.4 mL, 20 mmol) were added. The reaction was stirred at seventy degrees Celsius for three hour and then concentrated in vacuo. The residue was taken up in ethyl acetate and filtered through Celite. The filtrate washed with water two times, saturated sodium chloride solution, dried over Na2SO4, filtered, and concentrated in vacuo. The product was recrystallized (methanol) to give the N-pyrimidinyl piperidine sulfonamide as a white solid (4.51 g, 76%). The system was purged with nitrogen for 10 minutes The nitrogen stream was removed palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added The reaction was refluxed for forty five minutes cooled filtered through Celite under nitrogen concentrated in vacuo concentrated in vacuo filtered through Celite The filtrate washed with water two times, saturated sodium chloride solution dried over Na2SO4 filtered concentrated in vacuo The product was recrystallized (methanol)

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

Procedure: To a slurry of the piperidine sulfonamide from part F (6.3 g, 12.0 mmol) in methanol (25 mL) was added ammonium formate (2.2 g, 34.5 mmol). The system was purged with nitrogen for 10 minutes. The nitrogen stream was removed and palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added. The reaction was refluxed for forty five minutes, cooled, filtered through Celite under nitrogen, and concentrated in vacuo. The residue (6.21 g, 13.8 mmol) was dissolved in dry dimethylformamide (28 mL) and potassium carbonate (5.7 g, 41.4 mmol) and 2-chloropyrimidine (3.16 g, 27.6 mmol) were added. The reaction was stirred at eighty five degrees Celsius for one hour and then concentrated in vacuo. The residue was taken up in ethyl acetate and filtered through Celite. The filtrate washed with water two times, saturated sodium chloride solution, dried over Na2SO4, filtered, and concentrated in vacuo. The product was recrystallized (methanol) to give the N-pyrimidinyl piperidine sulfonamide as a white solid (4.94 g, 68%). The system was purged with nitrogen for 10 minutes The nitrogen stream was removed palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added The reaction was refluxed for forty five minutes cooled filtered through Celite under nitrogen concentrated in vacuo concentrated in vacuo filtered through Celite The filtrate washed with water two times, saturated sodium chloride solution dried over Na2SO4 filtered concentrated in vacuo The product was recrystallized (methanol)

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

Procedure: To a slurry of the piperidine sulfonamide from part F (420 mg, 0.8 mmol) in methanol (15 mL) was added ammonium formate (147 mg, 2.3 mmol). The system was purged with nitrogen for 10 minutes. The nitrogen stream was removed and palladium on carbon (80 mg of 10 weight % on activated carbon, 50% water) was added. The reaction was refluxed for forty five minutes, cooled, filtered through Celite under nitrogen, and concentrated in vacuo. The residue was dissolved in dry dimethylformamide (5 mL) and potassium carbonate (150 mg, 1.07 mmol) and 2-bromoethyl methyl ether (100 mL, 1.07 mmol) were added. The reaction was stirred at thirty five degrees Celsius for thirty hours and then concentrated in vacuo. The residue was taken up in ethyl acetate and filtered through Celite. The filtrate washed with water two times, saturated sodium chloride solution, dried over Na2SO4, filtered, and concentrated in vacuo. The product was recrystallized (methanol) to give the N-methoxyethyl piperidine sulfonamide as an off-white solid (190 mg, 53%). The system was purged with nitrogen for 10 minutes The nitrogen stream was removed palladium on carbon (80 mg of 10 weight % on activated carbon, 50% water) was added The reaction was refluxed for forty five minutes cooled filtered through Celite under nitrogen concentrated in vacuo The residue was dissolved in dry dimethylformamide (5 mL) concentrated in vacuo filtered through Celite The filtrate washed with water two times, saturated sodium chloride solution dried over Na2SO4 filtered concentrated in vacuo The product was recrystallized (methanol)

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

Procedure: This compound is obtained in 75% yield in a crude form from a mixture of equimolar quantities of diphenyl phenylphosphonite, acetaldehyde, and piperidinosulfonylamine in chlorobenzene. Recrystallization of a portion twice from acetonitrile gives a white solid product: mp 152°-165°; 31P nmr(DMSO-d6) -38.4 ppm. This compound is obtained in 75% yield in a crude form Recrystallization of a portion twice from acetonitrile gives a white solid product

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

Procedure: This compound is obtained in 75% yield in a crude form from a mixture of equimolar quantities of diphenyl phenylphosphonite, acetaldehyde, and piperidinosulfonylamine in chlorobenzene. Recrystallization of a portion twice from acetonitrile gives a white solid product: mp 152°-165°; 31P nmr(DMSO-d6) -38.4 ppm. This compound is obtained in 75% yield in a crude form Recrystallization of a portion twice from acetonitrile gives a white solid product

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

Procedure: This compound is obtained in 75% yield in a crude form from a mixture of equimolar quantities of diphenyl phenylphosphonite, acetaldehyde, and piperidinosulfonylamine in chlorobenzene. Recrystallization of a portion twice from acetonitrile gives a white solid product: mp 152°-165°; 31 p nmr(DMSO-d6) -38.4 ppm. This compound is obtained in 75% yield in a crude form Recrystallization of a portion twice from acetonitrile gives a white solid product

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Part G: Preparation of methyl 1-(5-ethyl-2-pyrimidinyl)-4-[[4-[4-(trifluoromethyl)-phenoxy]-1-piperidinyl]sulfonyl]-4-piperidinecarboxylate. To a slurry of the piperidine sulfonamide from part F (6.3 g, 12.0 mmol) in methanol (25 mL) was added ammonium formate (2.2 g, 34.5 mmol). The system was purged with nitrogen for 10 min. The nitrogen stream was removed and palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added. The reaction was refluxed for forty five min, cooled, filtered through Celite under N2, and concentrated in vacuo. The residue (4.5 g, 10 mmol) was dissolved in dry dimethylformamide (20 mL) and potassium carbonate (3.45 g, 325 mmol) and 2-chloro-5-ethylpyrimidine (1.82 mL, 15 mmol) were added. The reaction was stirred at 80° C. for four hr and then concentrated in vacuo. The residue was taken up in ethyl acetate and filtered through Celite. The filtrate washed with water two times, saturated sodium chloride solution, dried over Na2SO4, filtered, and concentrated in vacuo. The product was recrystallized (methanol) to give the N-pyrimidinyl piperidine sulfonamide as a white solid (3.33 g, 60%). The system was purged with nitrogen for 10 min The nitrogen stream was removed palladium on carbon (1.2 g of 10 weight % on activated carbon, 50% water) was added The reaction was refluxed for forty five min cooled filtered through Celite under N2 concentrated in vacuo concentrated in vacuo filtered through Celite The filtrate washed with water two times, saturated sodium chloride solution dried over Na2SO4 filtered concentrated in vacuo The product was recrystallized (methanol)