Sodium Bicarbonate → 7-[({1-[(4,9-Dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl)methyl]-4-piperidinyl}amino)methyl]-2,3-dihydro-1,4-benzodioxin-5-carbonitrile hydrochloride

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Reaction Steps

1-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (2:1 mixture of R:S) (60 mg, 0.2 mmol) and 7-formyl-2,3-dihydro-1,4-benzodioxin-5-carbonitrile (for a synthesis see WO06014580 Preparation 13 or WO2007122258 Example 31(d)) (37.8 mg, 0.2 mmol) were dissolved in dichloromethane/methanol (2/0.1 ml) at room temperature under argon and stirred at room temperature for 1 h. This was then treated with NaBH(OAc)3 (85 mg, 0.4 mmol) and left to stir for 1 hour. A saturated solution of sodium bicarbonate (15 ml) was then added and the aqueous was extracted with 20% methanol/dichloromethane (3×35 ml). The combined organic extracts were dried on magnesium sulphate, filtered and evaporated. The crude was purified by silica chromatography using a 0-20% methanol/dichloromethane gradient to provide the free base of the title compound as a pale yellow gum (26 mg, 27%).

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