Trifluoroacetic acid → HCID 178494211, compound

Participants

Reaction Steps

A mixture of tert-butyl 4-((1R)-1-(6-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate (0.450 g, 0.695 mmol) and trifluoroacetic acid (0.803 mL, 10.42 mmol) in DCM (25 mL) was treated with trifluoromethanesulfonic acid (0.01 mL) and allowed to stir under inert atmosphere for 1 h. The mixture was concentrated in vacuo. The residue was diluted with DCM (10 mL), then sodium carbonate (2.50 g) was added to the mixture and allowed to stir 10 min. Then methanesulfonyl chloride (0.271 mL, 3.47 mmol) was added slowly via syringe into the mixture. The mixture was allowed to stir under inert atmosphere overnight. The mixture was diluted with dichloromethane (20 mL), water (20 mL) and brine solution (10 mL). The organic layer was extracted with dichloromethane (3×15 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 10 micron, C18(2), 100 Å, 250×50 mm, (Varian, 5-70% acetonitrile in water with trifluoroacetic acid additive 0.1% v/v in each solvent) and then further purified by normal phase silica-gel chromatography on an Interchim puriflash (25 g) column eluting with 10% methanol in dichloromethane to give N-(5-fluoro-6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((R)-1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-amine (0.010 g, 0.018 mmol, 2.66% yield) as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δ 12.69 (s, 1H) 9.77 (d, J=1.96 Hz, 1H) 8.39 (dd, J=12.52, 2.15 Hz, 1H) 8.32 (d, J=2.15 Hz, 1H) 8.21 (s, 1H) 8.11 (d, J=2.15 Hz, 1H) 4.04 (s, 3H) 3.67-3.73 (m, 1H) 3.26 (t, J=4.69 Hz, 4H) 2.94 (s, 3H) 2.77 (s, 3H) 2.62-2.71 (m, 4H) 1.51 (d, J=6.65 Hz, 3H). m/z (ESI, +ve ion) 542.1 (M+H)+.

Provenance & Evidence