2-hex-5-ynylisoindole-1,3-dione

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

Procedure: In a manner similar to Description 1 (iii) and (iv), reaction of N-5-hexynylphthalimide, paraformaldehyde and pyrrolidine, followed by treatment with hydrazine hydrate gives 7-pyrrolidinohept-5-ynylamine.

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

Procedure: In a manner similar to Description 1 (iii) and (iv) reaction of N-5-hexynylphthalimide, paraformaldehyde and dimethylamine, followed by treatment with hydrazine hydrate gave the title compound b.p. 110°-20° C. (0.3 mm Hg).

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

Procedure: To potassium phthalimide (37.5 g) in dimethylformamide (400 ml) at 100° C,. was added dropwise 1-chloro-5-hexyne (23.67 g) in dimethylformamide (100 ml). The reaction mixture was stirred at 100° C. for a further hour, cooled and stirred at room temperature overnight. The mixture was poured on to ice/water to give an oil, which on trituration gave as a white solid N-5-hexynyl phthalimide (18.35 g), m.p. 74°-6° C. (recrystallisation from ethanol). at 100° C cooled stirred at room temperature overnight to give an oil, which on trituration

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

Procedure: To potassium phthalimide (37.5 g) in dimethylformamide (400 ml) at 100° C,. was added dropwise 1-chloro-5-hexyne (23.67 g) in dimethylformamide (100 ml). The reaction mixture was stirred at 100° C. for a further hour, cooled and stirred at room temperature overnight. The mixture was poured on to ice/water to give an oil, which on trituration gave as a white solid N-5-hexynyl phthalimide (18.35 g), m.p. 74°-6° C. (recrystallisation from ethanol). at 100° C cooled stirred at room temperature overnight to give an oil, which on trituration

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A screw-cap tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine (105 mg, example 37), tetrakis(triphenylphosphine)palladium (52 mg), copper(I) iodide (26 mg), N-5-hexynylphthalimide (186 mg), triethylamine (400 μL) and 1-methyl-2-pyrrolidinone (4 mL). The tube is evacuated, filled with argon and sealed. After stirring at 90° C. for 14 h, the mixture is diluted with water and the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5) to give 2-(6-{3-[(1-methylpiperidin-4-yloxy)-pyridin-2-ylmethyl]phenyl}hex-5-ynyl)isoindole-1,3-dione as an brown oil. The tube is evacuated filled with argon sealed the mixture is diluted with water the aqueous phase is extracted with ethyl acetate The pooled organic extracts are washed with water dried over magnesium sulfate concentrated under reduced pressure The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)

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

Procedure: In a manner similar to Description 1 (iii) and (iv), reaction of N-5-hexynylphthalimide, paraformaldehyde and pyrrolidine, followed by treatment with hydrazine hydrate gives 7-pyrrolidinohept-5-ynylamine.

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

Procedure: To potassium phthalimide (37.5 g) in dimethylformamide (400 ml) at 100° C. was added dropwise 1-chloro-5-hexyne (23.67 g) in dimethylformamide (100 ml). The reaction mixture was stirred at 100° C. for a further hour, cooled and stirred at room temperature overnight. The mixture was poured on to ice/water to give an oil, which on trituration gave as a white solid N-5-hexynyl phthalimide (18.35 g), m.p. 74°-6° C. (recrystallisation from ethanol). cooled stirred at room temperature overnight to give an oil, which on trituration

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

Procedure: In a manner similar to Description 1 (iii) and (iv), reaction of N-5-hexynylphthalimide, paraformaldehyde and pyrrolidine, followed by treatment with hydrazine hydrate gives 7-pyrrolidinohept-5-ynylamine.

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

Procedure: In a manner similar to Description 1 (iii) and (iv) reaction of N-5-hexynylphthalimide, paraformaldehyde and dimethylamine, followed by treatment with hydrazine hydrate gave the title compound b.p. 110°-20° C. (0.3 mm Hg).

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

Procedure: To potassium phthalimide (37.5 g) in dimethylformamide (400 ml) at 100° C,. was added dropwise 1-chloro-5-hexyne (23.67 g) in dimethylformamide (100 ml). The reaction mixture was stirred at 100° C. for a further hour, cooled and stirred at room temperature overnight. The mixture was poured on to ice/water to give an oil, which on trituration gave as a white solid N-5-hexynyl phthalimide (18.35 g), m.p. 74°-6° C. (recrystallisation from ethanol). at 100° C cooled stirred at room temperature overnight to give an oil, which on trituration

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A screw-cap tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]pyridine (105 mg, example 37), tetrakis(triphenylphosphine)palladium (52 mg), copper(I) iodide (26 mg), N-5-hexynylphthalimide (186 mg), triethylamine (400 μL) and 1-methyl-2-pyrrolidinone (4 mL). The tube is evacuated, filled with argon and sealed. After stirring at 90° C. for 14 h, the mixture is diluted with water and the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5) to give 2-(6-{3-[(1-methylpiperidin-4-yloxy)-pyridin-2-ylmethyl]phenyl}hex-5-ynyl)isoindole-1,3-dione as an brown oil. The tube is evacuated filled with argon sealed the mixture is diluted with water the aqueous phase is extracted with ethyl acetate The pooled organic extracts are washed with water dried over magnesium sulfate concentrated under reduced pressure The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)

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

Procedure: In a manner similar to Description 1 (iii) and (iv), reaction of N-5-hexynylphthalimide, paraformaldehyde and pyrrolidine, followed by treatment with hydrazine hydrate gives 7-pyrrolidinohept-5-ynylamine.