Ammonium Chloride → 3-Phenoxy-5-(pyridin-2-ylthio)pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

A nitrogen purged flask was charged with 5-bromo-3-phenoxypyridin-2-amine (5.00 g, 18.9 mmol) and THF (80 mL) and cooled to −78° C. Methyllithium (14.1 mL, 22.6 mmol) was added and stirred for 5 minutes. Butyllithium (9.05 mL, 22.6 mmol) was added and the reaction was stirred for 10 minutes at −78° C. (solids precipitated). 2-(2-(Pyridin-3-yl)disulfanyl)pyridine (10.4 g, 47.2 mmol) was added and the reaction was warmed to ambient temperature and stirred for 18 hours. The reaction was poured into saturated aqueous NH4Cl and extracted with EtOAc, dried over sodium sulfate, filtered and concentrated. The residue was dissolved in methanol and NaBH4 (excess) was added and stirred for 10 minutes. The reaction was poured into saturated aqueous NH4Cl and extracted with EtOAc (2×75 mL). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica (100% EtOAc to 1% methanol in EtOAc) to afford crude product. The material was dissolved in 2% MeOH in CH2Cl2 and washed with 1N NaOH. The organic layer was separated, dried, filtered, and concentrated to give 3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-amine (10.4 g, 47.2 mmol).

Provenance & Evidence