A solution of primary amine (1.0 eq.), paraformaldehyde (2.2 eq.) and acetic acid (1.0 eq.) in MeOH in a sealed tube was stirring at room temperature under Ar for 30 min. A solution of bicyclic piperidone (1.0 eq.) and acetic acid (1.0 eq.) was added to the previous reaction mixture. The reaction mixture was heated to reflux for 16 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. The residue was added 50% KOH(aq.) (5 mL) followed by DCM (10 mL) to dissolve all the oil. The two layers were separated and extracted with DCM (15 mL × 2). The combined organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to give the crude product as a yellow oil. The crude product was purified by a sequence of procedures: First, the crude product was dissolved in DCM and neutral alumina was added. The solvent was evaporated under reduced pressure, and PE was added to the residue. The mixture was stirring at room temperature for 1 hour. The solvent was discarded and fresh PE was added until the impurity was removed. Then a mixture of PE/DCM (1:5 to 1:3) was added and repeat the process described above until the product was found in the organic phase. The last solvent was retained and evaporated under reduced pressure. The product was purified by flash column chromatography on neutral alumina to give a pale-yellow oil with purities over 90%(w/w). The product such as N-PMB diamine piperidone was dissolved in a minimal amount of ethanol. A double volume of PE was added to the solution. The solution was naturally volatilized at room temperature to give the pure product of N-PMB diamine ketone with purities over 99%(w/w) as a colorless needle-like solid or cubic crystal. in diethylene glycol (10 mL) was added 50% (w/v) hydrazine hydrate (1.8 g, 18 mmol, 5.0 eq.). The reaction mixture was heated to 160 o C under Ar for 16 hours. After the reaction was completed, water (10 mL) was added to the mixture at 80 o C and the solution was neutralized with 1 N HCl (10 mL). The aqueous phase was extracted with MTBE (25 mL × 3) and then the water phase was adjusted to pH=12 by using potassium hydroxide. The aqueous phase was extracted with MTBE (25 mL × 3). The combined organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude product was purified by flash column chromatography on neutral alumina using MeOH/DCM (1-3%) to give the N-PMB tricyclic diamine as a white solid (724 mg, 67%).