piperidine-1-carbonitrile

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:

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

実験手順: Amidine (e) is readily produced from nitrites. More specifically, hydroxylamine hydrochloride dissolved in a suitable solvent, such as water, is reacted with cyanopiperidine (g) in the presence of a base such as sodium carbonate in a suitable solvent, such as in methanol and exposed to heat to provide the hydroxycarbamimidoyl-piperidine (h). The hydroxycarbamimidoylpiperidine (h) in a suitable solvent, such as acetic acid, is then hydrogenated via palladium catalyst in the presence of acetic acid anhydride under pressure to provide amidine (e). to heat

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

実験手順: 4-Chlorophenylacetonitrile was reacted with three equivalents of sodium hydride and one equivalent of N-tert-butyloxycarbonyl-bis-(2-chloroethyl)amine in DMF, initially at room temperature and then at 60° C. to give, after work up, the N-protected piperidine nitrile title compound. at 60° C. to give

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

実験手順: A solution of 45.2 g. (0.41 mole) of 1-piperidinecarbonitrile and 11 g. (0.05 mole) of a 25% solution of sodium methoxide in methanol in 200 ml. of methanol is stirred at room temperature under a nitrogen atmosphere for 18 hours. The solvent is evaporated and the residue is taken up in ether. The ether solution is filtered through a small pad of Celite and evaporated to constant weight to give 57.8 g. (99%) of a colorless oil. The solvent is evaporated The ether solution is filtered through a small pad of Celite evaporated to constant weight to give 57.8 g

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(N-hydroxycarbamimidoyl)-pyrazin-2-yl]-propionamide (prepared as in Example 1, 7.00 g, 15.02 mmol) in N-cyanopiperidine (25 mL) was heated at 130° C. in a sealed tube for 1.5 h. The mixture was allowed to cool to 25° C. and then concentrated under a stream of anhydrous nitrogen overnight. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/2 ethyl acetate/hexanes) afforded the N-[5-(5-amino-[1,2,4]oxadiazol-3-yl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (2.74 g, 37%) as an off-white solid: mp 262–264° C.; (ES)+-HRMS m/e calcd for C21H23ClN6O4S2 (M+Na)+ 513.1082, found 513.1088. to cool to 25° C. concentrated under a stream of anhydrous nitrogen overnight

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

実験手順: Amidine (e) is readily produced from nitrites. More specifically, hydroxylamine hydrochloride dissolved in a suitable solvent, such as water, is reacted with cyanopiperidine (g) in the presence of a base such as sodium carbonate in a suitable solvent, such as in methanol and exposed to heat to provide the hydroxycarbamimidoyl-piperidine (h). The hydroxycarbamimidoylpiperidine (h) in a suitable solvent, such as acetic acid, is then hydrogenated via palladium catalyst in the presence of acetic acid anhydride under pressure to provide amidine (e). to heat

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

実験手順: Amidine (e) is readily produced from nitrites. More specifically, hydroxylamine hydrochloride dissolved in a suitable solvent, such as water, is reacted with cyanopiperidine (g) in the presence of a base such as sodium carbonate in a suitable solvent, such as in methanol and exposed to heat to provide the hydroxycarbamimidoyl-piperidine (h). The hydroxycarbamimidoylpiperidine (h) in a suitable solvent, such as acetic acid, is then hydrogenated via palladium catalyst in the presence of acetic acid anhydride under pressure to provide amidine (e). to heat

反応条件: temp:0.00; pressure:0.00; stir: