Hydrochloric Acid → tert-butyl 2-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}pyrrolidine-1-carboxylate

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Reaction Steps

To a solution of 2-amino-9H-pyrido[2,3-b]indole-3-carboxamide (5, 50 mg, 0.2 mmol) in N,N-dimethylformamide (0.5 mL) was added powdered sodium hydroxide (12 mg, 0.31 mmol) and tetrabutylammonium hydrogen sulfate (3 mg, 0.009 mmol). The mixture was stirred at room temperature for 30 min then tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate (67 mg, 0.25 mmol) was added. The resulting mixture was stirred at room temperature for 4 days. Water (5 ml) was added to the mixture, followed by HCl (3% aqueous, 1 mL). The mixture was extracted with ethyl acetate (3×30 ml). The extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (12 g silica, methylene chloride to 90/10 methylene chloride/methanol gradient) to yield tert-butyl 2-{[2-amino-3-(aminocarbonyl)-9H-pyrido[2,3-b]indol-9-yl]methyl}pyrrolidine-1-carboxylate (xvi-e, 20 mg, 20%). NH4OAc QC conditions. M+1=410.

Provenance & Evidence