3-piperidin-1-ylpropan-1-ol

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:

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: To a stirred solution of 3-piperidin-1-yl-propan-1-ol (0.85 mmol, 121 mg) in THF at room temperature, NaH (1.2 mmol, 29 mg) was added and stirring continued for 10 min then 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (Example 1, 0.42 mmol, 150 mg) was added. The resulting mixture was stirred at 50-55° C. over night, poured into water and extracted with ethyl acetate. The organic layer was washed with water, brine dried (Na2SO4) filtered and concentrated under reduced pressure. The product was purified by column chromatography using 10% methanolic solution of ammonia (2.0 M ammonia in methanol) in DCM to get 4-(4-Benzyloxy-phenyl)-3-butyl-6-(3-piperidin-1-yl-propoxy)-pyridazine. The resulting mixture was stirred at 50-55° C. over night extracted with ethyl acetate The organic layer was washed with water, brine dried (Na2SO4) filtered concentrated under reduced pressure The product was purified by column chromatography

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

Procedure: Diketene (1.48 mL, 19.2 mmol, 1.30 equiv) was added to a solution of 1-(3-hydroxypropyl)piperidine (2.12 g, 14.8 mmol, 1.00 equiv, Leonard, N. J.; Musker, W. K. J. Am. Chem. Soc. 1960, 82, 5148) in toluene (30 mL), and the mixture was stirred under argon for 72 hours at room temperature. Removal of solvent gave 3.52 g (100%) of light brown, viscous oil, which was characterized spectroscopically and used for the next reaction without purification. Removal of solvent gave 3.52 g (100%) of light brown used for the next reaction without purification

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2-Chloro-4-fluorobenzonitrile (5.0 g) and 3-(1-piperidinyl)-1-propanol (3.4 g) were stirred in DMSO (70 ml) at rt under argon. Sodium hydride (60% wt in mineral oil, 1.976 g) was then added and the reaction stirred at rt for 5 h. The reaction mixture was diluted with ethyl acetate (200 ml), washed with saturated sodium hydrogen carbonate (100 ml), water (3×100 ml), brine (100 ml), dried (MgSO4) and evaporated. The crude product was then purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)] and fractions containing pure product were combined and evaporated to give the title compound (D26) as a white solid (6.29 g). MS electrospray (+ion) 279/281 (MH+). washed with saturated sodium hydrogen carbonate (100 ml), water (3×100 ml), brine (100 ml) dried (MgSO4) evaporated The crude product was then purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)] and fractions containing pure product evaporated

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

Procedure: 2-Chloro-4-fluorobenzonitrile (5.0 g) and 3-(1-piperidinyl)-1-propanol (3.4 g) were stirred in DMSO (70 ml) at rt under argon. Sodium hydride (60% wt in mineral oil, 1.976 g) was then added and the reaction stirred at rt for 5 h. The reaction mixture was diluted with ethyl acetate (200 ml), washed with saturated sodium hydrogen carbonate (100 ml), water (3×100 ml), brine (100 ml), dried (MgSO4) and evaporated. The crude product was then purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)] and fractions containing pure product were combined and evaporated to give the title compound (D26) as a white solid (6.29 g). MS electrospray (+ion) 279/281 (MH+). washed with saturated sodium hydrogen carbonate (100 ml), water (3×100 ml), brine (100 ml) dried (MgSO4) evaporated The crude product was then purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)] and fractions containing pure product evaporated