Aldol condensation of 5-bromo-2-propoxybenzaldehyde (I) with 4'-chloroacetophenone in the presence of NaOH produced chalcone (III) (1), which was condensed with pyridine-4-carbaldehyde (IV) using NaCN as the catalyst to yield diketone (V). Finally, the target pyrrole was constructed by Paal-Knorr synthesis using diketone (V) and ammonium acetate in boiling AcOH.
The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromobenzyl bromide (II) in the presence of n-butyllithium, followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III). Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V), which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI). Finally, Suzuki coupling of (VI) with 3-methoxybenzeneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.
The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromo-2-fluorobenzyl bromide (II) in the presence of n-butyllithium, followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III). Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V), which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI). Finally, Suzuki coupling of (VI) with 5-butyl-2-thiopheneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.
Addition of methyl propiolate (I) to 2,4-hexadienal (II) using lithium hexamethyldisilazide afforded diene (III). Subsequent cycloaddition of (III) to 4-phenyl urazole (IV) in the presence of iodobenzene diacetate produced the corresponding triazolopyridazine as a diastereomeric mixture, from which the required cis isomer was isolated by flash chromatography.