Water → 4-(2-(4-Aminonaphthalen-1-yl)ethoxy)pyridin-2-amine

Participants

Reaction Steps

To a degassed suspension of tert-butyl 4-(2-(2-chloropyridin-4-yloxy)ethyl)naphthalen-1-ylcarbamate (33) (600 mg, 1.50 mmol), tert-butyl carbamate (176 mg, 1.50 mmol), Cs2CO3 (733 mg, 2.26 mmol) and Xathphos (43 mg, 0.075 mmol) in THF (10 mL) was added Pd2dba3 (34 mg, 0.038 mmol) and the reaction mixture was heated at reflux under nitrogen for 16 hr. Water was added and the reaction mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 0-50% hexane in ethyl acetate, gradient elution) to afford a mixture of the desired Boc protected product and starting material, which was dissolved in a mixture of DCM (2 mL) and TFA (2 mL) and stirred at RT for 1 hr. The solvent was evaporated in vacuo and the residue was dissolved in DCM and washed with saturated aqueous NaHCO3 solution and brine, then dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 5% MeOH in DCM, isocratic elution) to afford the title compound (34) (45 mg, 11%); m/z 280 (M+H)+, (ES+).

Provenance & Evidence