Cesium carbonate → (S)-N4-(1-(5-Fluoropyridin-2-yl)ethyl)-N2-(2-methoxypyridin-3-yl)pyrimidine-2,4-diamine

Participants

Reaction Conditions

Reaction Steps

An oven-dried resealable Schlenk tube was charged with (S)-2-chloro-N-(1-(5-fluoropyridin-2-yl)ethyl)pyrimidin-4-amine (Preparation 1a, 43 mg, 0.17 mmol), 2-methoxypyridin-3-amine (23 mg, 0.19 mmol), cesium carbonate (111 mg, 0.34 mmol) and 1,4-dioxane (3 mL). The Schlenk tube was subjected to three cycles of evacuation-backfilling with argon then tris(dibenzylideneacetone)dipalladium(0) (16 mg, 0.02 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (10 mg, 0.02 mmol) were added. After three further cycles of evacuation-backfilling with argon, the Schlenk tube was capped and then stirred and heated to 100° C. After 24 hours the mixture was cooled to ambient temperature and the solvent was evaporated under reduced pressure. Ethyl acetate was added and the organic solution was washed with water (×3) and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to give the title compound (11 mg, 19%) as a solid.

Provenance & Evidence