Sodium hydride → 3-[2-(2-Tert-butoxycarbonylmethyl-1-cyclohexenyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

Participants

Reaction Steps

To a suspension of sodium hydride (44.2 g, 60% oil) in toluene (5.6 l) was added carefully tert-butyl (diethoxyphosphoryl)acetate (278.3 g) at 0° C. under nitrogen atmosphere. After being stirred for 30 minutes, to a reaction mixture was added by portions 3-[2-(2-oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (282.7 g), and which was stirred for additional 68 hours at ambient temperature. A reaction mixture was poured into ice-water (3 l) and organic layer was separated. Aqueous layer was reextracted with ethyl acetate (2 l). Organic layer was combined, washed In turn with water (2 l×3) and saturated sodium chloride in water, and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (270-400 mesh, 7 Kg) eluting in turn with 9%, 17% and 33% ethyl acetate in toluene. Fractions containing another isomer were further purified under the same conditions (silica gel 1 kg). Fractions containing each of desired products were collected and concentrated in vacuo to give 3-[2-{2-(tert-butoxycarbonylmethyl)-1-cyclohexenyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo-[1,5-a]pyridine (252.9 g), 3-[2-{2-(tert-butoxycarbonylmethyl)-2-cyclohexen-1-yl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (31.68 g) and (E)-3-[2-{2-(tert-butoxycarbonylmethylene)cyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (16.08 g) respectively.

Provenance & Evidence