A suspension of (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride (for a preparation see Example 5A(j)) (60 mg, 0.161 mmol) in chloroform (2 ml) and methanol (0.100 ml) at rt under argon was treated with triethylamine (0.067 ml, 0.482 mmol) and stirred at rt for 15 h. The solution was then treated with 2,3-dihydro-1,4-benzodioxin-6-carbaldehyde (commercially available) (23.75 mg, 0.145 mmol) and stirred for a further 30 min. The solution was then treated with sodium triacetoxyborohydride (102 mg, 0.482 mmol) and stirred at rt for 30 min, LC-MS after 30 min showed some starting material present, more sodium triacetoxyborohydride (19 mg) was added, the reaction was stirred for 15 min. This was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×25 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM) to give the title compound as the free base (48 mg, 67%) as a yellow gum.
