Methyl iodide → 1,8-Naphthyridine

Beteiligte Stoffe

Reaktionsschritte

4,7-Dioxo-1,4,7,8-tetrahydro[1,8]naphthyridine-3-carboxamide. The preparation of specific examples of heterocycle W16.1 is described in Chart BE. 2-Amino-4-bromopyridine BE.1 is reacted with Boc-anhydride in dichloromethane toafford BE.2. The resulting Boc-protected amine is then oxidized with peroxybenzoic acid (Justus Liebigs Ann. Chem. 1972, 758, 111) to afford hydroxypyridine BE.3. The pyridyl nitrogen is then alkylated in the presence of potassium carbonate and iodomethane with acetone as solvent to afford BE.4. The Boc group is then removed under standard deprotection condition to afford BE.5. The pyrimidone BE.5 is then cyclized with methyl 2-(((4-chlorobenzyl)amino)carbonyl)-3-methoxy-2-propenoate to afford naphthyridine BE.6. Reaction of BE.6 with an alkylating agent (e.g. iodomethane) in the presence of potassium carbonate with acetone as solvent affords compounds such as BE.7. Compound BE.7 is then coupled through a modified Sonogashira coupling (Linstrumelle, G.; et. al, Tetrahedron Lett, 1993, 34 6403) with an electron-rich acetylene (e.g. propargyl alcohol, Z=CH2OH) to afford the alkyne derivative BE.8. Saturation of the alkyne by hydrogenation catalyzed by palladium on carbon in alcoholic solvents affords alkyl derivatives of formula BE.9 (Z=CH2OH).

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