4-methylpiperidin-4-amine

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: 2 ml of an ethanol suspension containing 260 mg of 4-amino-4-methylpiperidine (synthesized according to a method described in U.S. Pat. No. 5,821,240), 237 mg of 2-chloropyrimidine and 858 mg of potassium carbonate was stirred at 50° C. for 12 hours. The reaction mixture was poured into water, and extracted with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300:10:1)] to obtain 259 mg of 4-amino-4-methyl-N-(2-pyrimidinyl)piperidine (Reference Example 8-1 in Table 9). synthesized extracted with chloroform The extract was washed with brine dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300:10:1)]

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

実験手順: 2 ml of an ethanol suspension containing 260 mg of 4-amino-4-methylpiperidine (synthesized according to a method described in U.S. Pat. No. 5,821,240), 237 mg of 2-chloropyrimidine and 858 mg of potassium carbonate was stirred at 50° C. for 12 hours. The reaction mixture was poured into water, and extracted with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300:10:1)] to obtain 259 mg of 4-amino-4-methyl-N-(2-pyrimidinyl)piperidine (Reference Example 8-1 in Table 9). synthesized extracted with chloroform The extract was washed with brine dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300:10:1)]

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 60° C. a mixture of 30.8 g (0.270 mol) of 4-methylpiperidin-4-ylamine and 100 ml of methanol is added dropwise to a suspension of 100 g (0.257 mol) of (3) in 690 ml of methanol. The mixture is stirred for 1 hour at 60° C., allowed to cool to 40° C., 280 ml of 2N sodium hydroxide solution are added and the resulting mixture is stirred for 3 hours at 60° C. Then 300 ml of methanol are distilled off and 600 ml of water are added. The mixture is stirred for 5 minutes at ambient temperature, filtered off and the residue is washed with 250 ml of water, 3 times 50 ml of acetone and 100 ml of methyl-tert-butylether and dried at 40° C. in vacuo. Yield: 100.5 g (92.2%), melting point 211.5° C. 400 MHz-1H-NMR (DMSO) (ppm)=8.55 br s, 1H, NH; 8.05 dd, 1H, aniline-H; 7.78 ddd, 1H, aniline-H; 7.47 t, 1H, aniline-H; 6.90 br s, 1H, NH; 4.28 s, 2H, CH2; 3.68 m, 2H, CH2; 3.45 m, 2H, CH2, 3.32 br s, 2H, NH2; 1.37 m, 4H, 2CH2; 1.05 s, 3H, CH3. to cool to 40° C. the resulting mixture is stirred for 3 hours at 60° C Then 300 ml of methanol are distilled off 600 ml of water are added The mixture is stirred for 5 minutes at ambient temperature filtered off the residue is washed with 250 ml of water, 3 times 50 ml of acetone and 100 ml of methyl-tert-butylether dried at 40° C. in vacuo 4.28 s, 2H, CH2 1.05 s, 3H, CH3

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

実験手順: The title compound was prepared from 7B and excess 4-amino-4-methylpiperidine (WO 9732880) by a route analogous to that used for the preparation of 7C. Analytical HPLC retention time=1.43 min. (YMC Xterra S7 C 18, 3.0×50 mm column, 10–90% aqueous methanol over 2 minutes containing 0.1% TFA, 5 mL/min, monitoring at 220 nm) and a LC/MS M++1=495.

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

実験手順: 2 ml of an ethanol suspension containing 260 mg of 4-amino-4-methylpiperidine (synthesized according to a method described in U.S. Pat. No. 5,821,240), 237 mg of 2-chloropyrimidine and 858 mg of potassium carbonate was stirred at 50° C. for 12 hours. The reaction mixture was poured into water, and extracted with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300′:10:1)] to obtain 259 mg of 4-amino-4-methyl-N-(2-pyrimidinyl)piperidine (Reference Example 8-1 in Table 9). synthesized extracted with chloroform The extract was washed with brine dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by silica gel flash column chromatography [solvent

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

実験手順: 2 ml of an ethanol suspension containing 260 mg of 4-amino-4-methylpiperidine (synthesized according to a method described in U.S. Pat. No. 5,821,240), 237 mg of 2-chloropyrimidine and 858 mg of potassium carbonate was stirred at 50° C. for 12 hours. The reaction mixture was poured into water, and extracted with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300:10:1)] to obtain 259 mg of 4-amino-4-methyl-N-(2-pyrimidinyl)piperidine (Reference Example 8-1 in Table 9). synthesized extracted with chloroform The extract was washed with brine dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by silica gel flash column chromatography [solvent: chloroform-methanol-aqueous ammonia (300:10:1)]