Chlorotrimethylsilane → Tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

To a stirred suspension of 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (3.0 g, 14 mmol) in tetrahydrofuran (75 mL) was added chlorotrimethylsilane (4.5 mL, 35 mmol) dropwise. The reaction mixture was stirred at room temperature for 3 hours and a 2M solution of 2-propylmagnesium chloride in THF (37 mL, 74 mmol) was added dropwise. After 3 hours, tert-butyl 3-oxopiperidine-1-carboxylate (5.6 g, 28 mmol) was added in one portion. The mixture was stirred at room temperature overnight at which time LC/MS indicated the reaction was complete. The reaction was poured over a mixture of ice and saturated aqueous ammonium chloride (500 mL). The mixture was allowed to warm to room temperature and was extracted with ethyl acetate (250 mL) four times. The combined organic layers were washed with saturated brine, dried over sodium sulfate and concentrated under reduced pressure. The crude solid was triturated with a 2:1 mixture of ethyl acetate:heptane to obtain the title compound (2 g) having the following physical data.

Provenance & Evidence