Cesium carbonate → 5-Fluoro-4-(4-methylpiperazin-1-yl)pyridin-3-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl carbamate (709.9 mg, 6.060 mmol), Cs2CO3 (3.291 g, 10.10 mmol), xantphos (146.1 mg, 0.2525 mmol), Pd2(dba)3 (231.2 mg, 0.2525 mmol) and 1-(3-chloro-5-fluoro-4-pyridyl)-4-methyl-piperazine (1.16 g, 5.050 mmol) in dioxane (11.60 mL) was heated at 110° C. for 1 h. At room temperature, tert-butyl carbamate (709.9 mg, 6.060 mmol), xantphos (146.1 mg, 0.2525 mmol) and Pd2(dba)3 (231.2 mg, 0.2525 mmol) was added and the mixture was further heated at 120° C. in the microwave for 1 h. The reaction mixture was then filtered through a celite pad and washed with methanol and the filtrate concentrated in vacuo. The residue was purified by column chromatography on silica, using the ISCO column companion system eluting with 0-10% MeOH/DCM. Product fractions were combined and concentrated in vacuo to yield 5-fluoro-4-(4-methylpiperazin-1-yl)pyridin-3-amine as a light brown viscous oil. (642 mg, 60%). MS (ES+) 211.1.

Provenance & Evidence