Sodium Hydroxide → N-(3-Iodo-4-methyl-phenyl)-6-[4-(4-methoxy-phenyl)-piperazin-1-yl]-nicotinamide

Participants

Reaction Conditions

Reaction Steps

4-methoxyphenyl piperazine dihydrochloride (110 mg, 0.41 mmol) was partitioned between CH2Cl2 and 2N aq. NaOH. The aqueous layer was extracted twice more with CH2Cl2 and the combined organic layer was dried and concentrated. The residue was dissolved in dioxane (6 mL). The solution was then treated with diisopropyl ethylamine (0.07 mL, 0.41 mmol), a catalytic amount of DMAP and 6-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide (50 mg, 0.13 mmol). The mixture was heated in a sealed tube at 120° C. for 22 hr. The mixture was then cooled, followed addition of another portion of 4-methoxyphenyl piperazine hydrochloride (110 mg, 0.41 mmol) and diisopropyl ethyl amine (0.14 mL, 0.82 mmol). The mixture was stirred at 120° C. for 3 more days then cooled and partitioned between EtOAc and aq. saturated Na2CO3. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was chromatographed on a silica gel column with 20-40% EtOAc in hexanes to afford the product. HRMS m/z calcd for C24H25N4O2I [M+H]+: 529.1095. Found: 529.1098.

Provenance & Evidence