Sodium Hydroxide → tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyl 1-(5-(5-(2-fluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (125 mg, 0.195 mmol) in THF (3 mL) was treated with NaOH 10N (0.195 mL, 1.948 mmol). The reaction was heated to reflux at 80° C. After 4 h, the solution was cooled to 23° C., concentrated in vacuo and purified by silica gel chromatography (eluent: 1-5% MeOH/DCM), affording tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (69 mg, 73%). MS (ESI, pos. ion) m/z: 488.2 (M+1). A solution of tert-butyl 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (64 mg, 0.131 mmol) in MeOH (3 mL) and DCM (0.500 mL) was treated with HCl, 36.5-38.0% (0.109 mL, 1.313 mmol). The reaction was heated to 50° C. After 2 h 30 min, the reaction was cooled to 23° C. and concentrated. The residue (as HCl salt) was free-based using a Silicycle Si-propylsulfonic acid ion exchange column (catalog # R51230B). The compound was diluted in MeOH and added to a pad of the resin (wetted and flushed with 10 mL MeOH). It was flushed with MeOH (50 mL), and then the product was “released” using 2.0 M NH3 in MeOH solution (50 ml). The final filtrate was concentrated, affording 1-(5-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-amine. MS (ESI, pos. ion) m/z: 388.3 (M+1).

Provenance & Evidence