Racemic lometrexol has been prepared.
The condensation of 1,3-dioxoindane-2-carboxylic acid ethyl ester (I) with m-anisidine (II) in refluxing toluene gives the corresponding amide (III), which is cyclized with polyphosphoric acid (PPA) at 120 C yielding 3-methoxy-6,7-dihydro-5H-indeno[2,1-c]quinoline-6,7-dione (IV). The reaction of (IV) with refluxing POCl3 affords the chloroketone (V), which is condensed with 2-(dimethylamino)ethylamine (VI) in pyridine at 100 C giving the aminoketone (VII). Finally, this compound is demethylated with concentrated HBr in refluxing acetic acid.