HOAt → (R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

Participants

Reaction Steps

(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine 16 (150 mg, 491 μmol), 4,4-difluorocyclohexanecarboxylic acid (88.7 mg, 540 μmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (113 mg, 589 μmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (80.2 mg, 589 μmol), sodium bicarbonate (82.5 mg, 982 μmol) were stirred in DMF (3 ml) for one hour. The reaction was then taken up in ethyl acetate (30 ml) and washed with aqueous K2CO3 (10%), water, and brine. The organic phase was dried (MgSO4) and evaporated to give an orange oil. Chromatography of the residue over silica with a gradient of hexane to 100% ethyl acetate gave (R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone 17 as a yellow solid. LC/MS m/z=452 (M+H+).

Provenance & Evidence