Phosphorus pentachloride → HCID 58329529, compound

Participants

Reaction Steps

To a solution of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxylic acid (200 mg, 1.00 mmol) in dry N,N-dimethylformamide (3 mL) were added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (417 mg, 1.10 mmol) and disopropylethyl amine (0.35 mL, 2.0 mmol), and tert-butyl 4-aminopiperidine-1-carboxylate (1.00 mmol). The reaction was stirred at room temperature and monitored by LC-MS. Upon completion, the mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL), sat. NaHCO3 solution (25 mL) and brine. The organic phase was separated and dried over sodium sulfate. After removing solvent, the crude product was purified by silica gel chromatography (EtOAc/Hexanes) to give the desired product tert-butyl 4-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxamido)piperidine-1-carboxylate (77) as a white solid. Mp=187-189° C., LC/MS [M+H]: 384.22. Step 2: Amide (77) (1 eq), was dissolved in dicholoromethane (15 mL/1 mmol) and phosphorus pentachloride (1 eq) was added. The mixture was stirred at ambient temperature for 2 hours then trimethylsilyl azide (8 eq) was added. Mixture was stirred at room temperature for additional 4 hours and reaction progress was followed by LC-MS. Upon completion, saturated NaHCO3 solution was added and the mixture was extracted with dicholoromethane (30 mL/mol), Combined organics were combined and dried Na2SO4 Solvent was removed and the crude product was purified by silica gel chromatography (EtOAc/Hexanes, 25-40% gradient) to give the desired product tert-butyl 4-(5-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-1H-tetrazol-1-yl)piperidine-1-carboxylate (78) as a solid. LC/MS [M+H]: 409.23. Step 3: Carbamate (78) (1 equivalent) was dissolved in dicholoromethane and HCl (20 equivalent, 4 M in dioxane) was added and stirred at room temperature for 2 to 4 hours. Concentration of the solution under reduced pressure gave the pure desired product 1-(1-(piperidin-4-yl)-1H-tetrazol-5-yl)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline hydrochloride (79) as a white solid Mp=198-200° C., LC/MS [M+H]: 309.18.

Provenance & Evidence