An efficient and general method for the synthesis of 3-Phosphorylated 4-Aminoquinolines from β-phosphine oxide and phosphonate enamines.

Article abstract of DOI:10.1016/S0040-4020(96)01173-8

An easy and efficient synthesis of 4-aminoquinolines substituted with a phosphine oxide 1. phosphine sulphide 13 and phosphonate 11 group in the 3-position is described. The key step is a regioselective addition of lithiated β-enamino phophine oxides 5 and phosphonate 6 to isocyanate and isothiocyanates to give functionalized amides 7, 8 and thioamide 12. Subsequent cyclization of these compounds with phosphorus oxychloride in the presence of triethylamine afforded the substituted 4-aminoquinolines 1, 11 and 13.