Having successfully developed the process for the preparation of the Mannich base ( ), the next step was to synthesise the final product 3. The synthesis of ADQ (3) was carried out in two steps from the intermediate 14, following the reported procedure which involved hydrolysis of the Mannich base followed by condensation with 4,7-DCQ (5) in situ. As with the preparation of the Mannich base, several reaction conditions were examined to find a robust process for the preparation of ADQ (3). For the first attempt the Mannich base (14) was refluxed in 20% HCl for 4 h at 80 °C followed by distillation of the excess HCl, and then condensation of 4,7-DCQ (5) in ethanol for 24 h to give ADQ (3) in 43% yield. In addition to the low yield obtained, this process required extra energy to distil out water from the reaction, thus, it would not be practical during scale-up of the process. The next attempt involved refluxing the Mannich base ( ) in a mixture of HCl/H2O/solvent for 3-5 h, where the solvent was either ethanol or isopropanol, followed by condensation with 4,7-DCQ (5). Table Entry 2 shows the reaction in ethanol produced a low yield of 10%, whereas isopropanol (Entry 3) resulted in an improved yield of 58%. When the same reaction conditions are attempted in the absence of an organic solvent (Entry 4), a yield of 53% was obtained. The next attempt involved subjecting the Mannich base (14) to hydrolysis in commercial grade HCl (32%) at 85 °C for 4 h to produce the amine (15), which after pH adjustment to 4, was condensed with 4,7-DCQ (5) in situ to afford the desired ADQ dihydrochloride dihydrate (3). Crude 3 was recrystallized from ethanol and rehydrated by refluxing in water followed by precipitation at cool conditions to obtain ADQ dihydrochloride dihydrate (3) in an excellent yield of 90% with USP quality. The HPLC chromatogram shows only a single peak at a retention time between 5-6 minutes, proving the absence of starting material (Figures &).