Chlorosuccinimide → methyl 3-chloro-1-(methoxycarbonylamino)-1H-pyrrole-2-carboxylate

Participants

Reaction Steps

Alternately, compounds of formula (I) can be synthesized by the general sequence shown in Scheme 3. Commercially available 5-methyl-3,4-dihydro-2H-pyrrole 13 was treated with N-chlorosuccinimide followed by sodium methoxide to generate methyl 3-chloro-1H-pyrrole-2-carboxylate 14. Compound 14 was N-aminated and the product 15 was acylated to yield methyl 3-chloro-1-(methoxycarbonylamino)-1H-pyrrole-2-carboxylate 16. Compound 16 was treated with ammonia to yield 5-chloropyrrolo[1,2-f][1,2,4]triazine-2,4-diol 17. Compound 10 can be obtained from 17 by transition metal mediated Suzuki cross-coupling reactions with boronic acids or esters. Compound 17 gave 2,4,5-trichloropyrrolo[1,2-f][1,2,4]triazine 18 on treatment with chlorinating agents for example, POCl3 and then displacement of the C4 chloro with amines gave regioselectively 19. Using different palladium reagent/ligand combinations we could achieve regioselective Suzuki cross-couplings at C2 and C5 to generate compounds of general formula (I).

Provenance & Evidence