合成路线1

Combining (3-aminopropyl)carbamic acid benzyl ester (CBZ-protected propylene diamine) (I) with 2-oxoethylphosphonic acid diethyl ester under reductive amination conditions in the presence of sodium cyanoborohydride gives the CBZ-protected phosphonoethyl-substituted propylene diamine (II). The condensation of (II) with 3,4-diethoxy-3-cyclobutene-1,2-dione at room temperature in ethanol leads to the squaric acid analog (III). Removal of the CBZ protecting group under catalytic transfer hydrogenation conditions followed by spontaneous cyclization provides the penultimate diethylphosphonate ester (IV), which is hydrolyzed in the presence of bromotrimethylsilane in refluxing 1,2-dichloroethane to yield the final product in 15% overall yield.