The lithium anion of ethyl methanesulfonate (I) was condensed with ethyl chlorophosphonate to produce the phosphonate (II), which was subsequently subjected to a Wittig reaction with 5-chlorotiophene-2-carboxaldehyde (III), yielding olefin (IV). After cleavage of the ethyl sulfonate of (IV) by means of tetrabutylammonium iodide, treatment with sulfuryl chloride afforded the intermediate sulfonyl chloride (V).
Iodination of 4-aminopyridine (VI), followed by protection with Boc2O, provided the N-Boc iodopyridine (VIII). Piperazinone (XI) was prepared by alkylation of 4-(benzyloxycarbonyl)-2-piperazinone (IX) with propargyl bromide (X). Palladium-catalyzed coupling of propargyl piperazinone (XI) with iodopyridine (VIII) furnished adduct (XII), which was subsequently cyclized to the pyrrolopyridine derivative (XIII) upon treatment with DBU. The benzyloxycarbonyl group of (XIII) was then cleaved by transfer hydrogenolysis to yield the intermediate piperazinone (XIV).
Coupling of piperazinone (XIV) with sulfonyl chloride (V) gave rise to the sulfonamide (XV). The N-Boc group of (XV) was finally cleaved by treatment with trifluoroacetic acid to afford the title compound.