Treatment of 1-methoxy-4-nitro-2-(trifluoromethyl)benzene (I) with 4-chlorophenoxyacetonitrile (II) in the presence of potassium tert-butoxide afforded the arylacetonitrile (III). Reductive cyclization of (III) upon treatment with H2 and Pd/C produced indole (IV), which was further reduced to indoline (V) with NaBH3CN and AcOH. Methyl ether cleavage in (V) using ISiMe3 yielded phenol (VI). After protection of the amino group of (VI) as the acetamide (VII), sulfonylation at the phenol group with trifluoromethanesulfonic anhydride and pyridine gave triflate (VIII). The triflate group was then displaced with tetramethyltin in the presence of palladium catalyst to furnish, after hydrolysis of the acetamide, the 5-methyl-6-(trifluoromethyl)indoline (IX).
Coupling of 3-hydroxypyridine (X) with 2-chloropyridine (XI) afforded the corresponding dipyridyl ether (XII). After reduction of the nitro group of (XII) with SnCl2, the resulting aminopyridine (XIII) was treated with phenyl chloroformate to give the phenyl carbamate (XIV). Finally, condensation of carbamate (XIV) with indoline (IX) produced the title carboxamide.
Reaction between 1-methoxy-4-nitro-2-trifluoromethylbenzene (I) and 4-chlorophenoxyacetonitrile (II) in the presence of potassium tert-butoxide produced aryl acetonitrile (III). Catalytic hydrogenation of (III) gave rise to indole (IV), which was further reduced to indoline (V) employing sodium cyanoborohydride and AcOH.