1-prop-2-ynylazepane

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

Procedure: 0.76 g of dichlorobis(triphenylphosphine)palladium are added, under an inert atmosphere, to 3.6 g of 1-prop-2-ynylazepane (compound 4.1), 8 g of [4-(4,4-dimethylcyclohexyl)-3-chlorophenyl]trifluoromethanesulphonate (compound III.1), 0.103 g of copper iodide, 1.83 g of lithium chloride in 200 ml of triethylamine and 100 ml of pyridine. The reaction mixture is heated at reflux for 12 hours. The solvents are evaporated off under reduced pressure and the residue obtained is purified by chromatography on a column of silica gel, eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture. The residue obtained is taken up in diethyl ether and the hydrochloride is formed by bubbling hydrochloric acid through. After filtration, the residue obtained is recrystallized from toluene. The reaction mixture is heated at reflux for 12 hours The solvents are evaporated off under reduced pressure the residue obtained is purified by chromatography on a column of silica gel eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture The residue obtained

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

Procedure: 0.76 g of dichlorobis(triphenylphosphine)palladium are added, under an inert atmosphere, to 3.6 g of 1-prop-2-ynylazepane (compound 4.1), 8 g of [4-(4,4-dimethylcyclohexyl)-3-chlorophenyl]trifluoromethanesulphonate (compound III.1), 0.103 g of copper iodide, 1.83 g of lithium chloride in 200 ml of triethylamine and 100 ml of pyridine. The reaction mixture is heated at reflux for 12 hours. The solvents are evaporated off under reduced pressure and the residue obtained is purified by chromatography on a column of silica gel, eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture. The residue obtained is taken up in diethyl ether and the hydrochloride is formed by bubbling hydrochloric acid through. After filtration, the residue obtained is recrystallized from toluene. The reaction mixture is heated at reflux for 12 hours The solvents are evaporated off under reduced pressure the residue obtained is purified by chromatography on a column of silica gel eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture The residue obtained

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

Procedure: 1.96 g of 1-prop-2-ynylazepane (compound 4.1) are added, under inert atmosphere, to 4 g of 4-bromo-2-chlorophenyl trifluoromethanesulphonate (compound IIIa.1), 0.062 g of copper iodide, 10 ml of pyridine and 20 ml of triethylamine, followed by 0.457 g of the catalyst dichlorobis(triphenylphosphine)palladium. The reaction mixture is heated at the reflux point for 2 hours, the solvents are evaporated off under reduced pressure, and the residue obtained is taken up in dichloromethane, washed in water and dried over magnesium sulphate. After evaporating off the solvents under reduced pressure, the residue obtained is purified by chromatography on a column of silica gel, eluting with an 80/20 cyclohexane/ethyl acetate mixture; m.p.=192° C. The reaction mixture is heated at the reflux point for 2 hours the solvents are evaporated off under reduced pressure the residue obtained washed in water dried over magnesium sulphate After evaporating off the solvents under reduced pressure the residue obtained is purified by chromatography on a column of silica gel eluting with an 80/20 cyclohexane/ethyl acetate mixture

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

Procedure: 1.96 g of 1-prop-2-ynylazepane (compound 4.1) are added, under inert atmosphere, to 4 g of 4-bromo-2-chlorophenyl trifluoromethanesulphonate (compound IIIa.1), 0.062 g of copper iodide, 10 ml of pyridine and 20 ml of triethylamine, followed by 0.457 g of the catalyst dichlorobis(triphenylphosphine)palladium. The reaction mixture is heated at the reflux point for 2 hours, the solvents are evaporated off under reduced pressure, and the residue obtained is taken up in dichloromethane, washed in water and dried over magnesium sulphate. After evaporating off the solvents under reduced pressure, the residue obtained is purified by chromatography on a column of silica gel, eluting with an 80/20 cyclohexane/ethyl acetate mixture; m.p.=192° C. The reaction mixture is heated at the reflux point for 2 hours the solvents are evaporated off under reduced pressure the residue obtained washed in water dried over magnesium sulphate After evaporating off the solvents under reduced pressure the residue obtained is purified by chromatography on a column of silica gel eluting with an 80/20 cyclohexane/ethyl acetate mixture

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

Procedure: 18.8 ml of a 3-bromopropyne solution at 80% in toluene are added dropwise to 20.8 ml of hexamethyleneamine and 27.9 g of potassium carbonate in 300 ml of acetonitrile. The reaction mixture is heated at 50° C. for 12 hours and 6 hours at 80° C. The reaction mixture is filtered, and the solvents are evaporated off under reduced pressure. Compound 4.1 is purified by distillation; b.p.=61° C. under a pressure of 26.7 Pa. The reaction mixture is filtered the solvents are evaporated off under reduced pressure Compound 4.1 is purified by distillation

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

Procedure: 0.76 g of dichlorobis(triphenylphosphine)palladium are added, under an inert atmosphere, to 3.6 g of 1-prop-2-ynylazepane (compound 4.1), 8 g of [4-(4,4-dimethylcyclohexyl)-3-chlorophenyl]trifluoromethanesulphonate (compound III.1), 0.103 g of copper iodide, 1.83 g of lithium chloride in 200 ml of triethylamine and 100 ml of pyridine. The reaction mixture is heated at reflux for 12 hours. The solvents are evaporated off under reduced pressure and the residue obtained is purified by chromatography on a column of silica gel, eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture. The residue obtained is taken up in diethyl ether and the hydrochloride is formed by bubbling hydrochloric acid through. After filtration, the residue obtained is recrystallized from toluene. The reaction mixture is heated at reflux for 12 hours The solvents are evaporated off under reduced pressure the residue obtained is purified by chromatography on a column of silica gel eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture The residue obtained

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

Procedure: 1.96 g of 1-prop-2-ynylazepane (compound 4.1) are added, under inert atmosphere, to 4 g of 4-bromo-2-chlorophenyl trifluoromethanesulphonate (compound IIIa.1), 0.062 g of copper iodide, 10 ml of pyridine and 20 ml of triethylamine, followed by 0.457 g of the catalyst dichlorobis(triphenylphosphine)palladium. The reaction mixture is heated at the reflux point for 2 hours, the solvents are evaporated off under reduced pressure, and the residue obtained is taken up in dichloromethane, washed in water and dried over magnesium sulphate. After evaporating off the solvents under reduced pressure, the residue obtained is purified by chromatography on a column of silica gel, eluting with an 80/20 cyclohexane/ethyl acetate mixture; m.p.=192° C. The reaction mixture is heated at the reflux point for 2 hours the solvents are evaporated off under reduced pressure the residue obtained washed in water dried over magnesium sulphate After evaporating off the solvents under reduced pressure the residue obtained is purified by chromatography on a column of silica gel eluting with an 80/20 cyclohexane/ethyl acetate mixture

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

Procedure: 18.8 ml of a 3-bromopropyne solution at 80% in toluene are added dropwise to 20.8 ml of hexamethyleneamine and 27.9 g of potassium carbonate in 300 ml of acetonitrile. The reaction mixture is heated at 50° C. for 12 hours and 6 hours at 80° C. The reaction mixture is filtered, and the solvents are evaporated off under reduced pressure. Compound 4.1 is purified by distillation; b.p.=61° C. under a pressure of 26.7 Pa. The reaction mixture is filtered the solvents are evaporated off under reduced pressure Compound 4.1 is purified by distillation