Formaldehyde → 1-[(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)methyl]piperidin-4-ol

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Reaction Steps

4-Hydroxypiperidine (3.62 g, 35.8 mmol) and 37% formalin solution (2.9 g, 35.8 mmol) were dissolved in acetic acid (150 mL) and stirred at room temperature for 1 h. To this solution was added a solution of pyrrolo[2,1-f][1,2,4]triazin-4-amine (2.0 g, 14.9 mmol; prepared according to the procedure described in WO 2007/056170-A2, Intermediate A) in acetic acid (150 mL), and the mixture was stirred at 60° C. for 2 h. The solvent was then evaporated, and the residue was taken up in 200 mL of half-concentrated aqueous potassium bicarbonate solution and extracted with 200 mL dichloromethane. The organic layer was washed with water (2×50 mL) and discarded. The combined aqueous layers were evaporated to dryness, and the residue was treated with a 10:1 mixture of dichloromethane and methanol (2×100 mL). The organic extracts were evaporated, and the residue was purified by preparative HPLC (method 4) to give 1.16 g (15% of th.) of the title compound.

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