Methanesulfonic Acid → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-tert-butyl (1-((9-chloro-7-fluoro-6-(4-methoxybenzyl)-4-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.08 g, 0.037 mmol) in TFA (8 mL) cooled to 0° C. was added methanesulfonic acid (0.243 μl, 3.75 μmol). The reaction mixture was then heated at 70° C. for 2 h. The volatiles were evaporated. The residue was taken up in water and neutralized with 10% aqueous NaHCO3. The solution was extracted with EtOAc (3×15 mL). The combined organic layers were washed with brine (1×15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Column: X-Bridge (19×150 mm) 5 μm, Flow rate: 15 ml/min; Solvent A: 0.01% TFA, Solvent B: ACN) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-chloro-7-fluoro-4-methylbenzo[c][2,7]naphthyridin-5(6H)-one, 3 TFA (9.5 mg, 0.013 mmol, 34.4% yield) as an off-white solid. LC/MS (ESI) m/e 378.0 [(M+H)+, calcd for C19H22ClFN3O2 378.1]; LC/MS retention time (method C): tR=2.02 min; HPLC retention time (method A): tR=7.47 min; HPLC retention time (method B): tR=8.41 min; 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.70 (d, J=6.0 Hz, 1H), 8.40 (d, J=2.0 Hz, 1H), 8.35 (d, J=6.3 Hz, 1H), 4.49 (dd, J=10.7, 2.6 Hz, 1H), 4.35 (dd, J=10.5, 5.8 Hz, 1H), 3.75-3.69 (m, 1H), 3.14 (s, 3H), 1.90-1.74 (m, 2H), 1.70-1.56 (m, 1H), 1.04 (d, J=2.3 Hz, 3H), 1.03 (d, J=2.5 Hz, 3H).

Provenance & Evidence