Hydrochloric Acid → (S)-8-((2-amino-4-methylpentyl)oxy)-6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridine-9-carbonitrile

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Reaction Conditions

Reaction Steps

In a 25 mL round-bottomed flask, (S)-tert-butyl (1-((9-cyano-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (75 mg, 0.167 mmol) was taken up in MeOH (4 mL) and cooled to 0° C. The mixture was treated with 4M solution of HCl in 1,4-dioxane (2 mL, 8 mmol) and stirred for 2 h at RT. The MeOH was removed and the crude product was dissolved in EtOAc (20 mL). The ethyl acetate layer was washed with water (2×10 mL) and dried over sodium sulfate. Removal of the solvent gave crude product which was purified by silica-gel column (MeOH—CHCl3 mixture) to obtain (S)-8-((2-amino-4-methylpentyl)oxy)-6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridine-9-carbonitrile (4 mg, 0.01 mmol, 7% yield over 2 steps) as a yellow solid. LC/MS (ESI) m/e 351.2. [(M+H)+, calcd for C20H23N4O2, 351.4]; LC/MS retention time (method B): tR=1.43 min. HPLC retention time (method A): tR=9.69 min; HPLC retention time (method B): tR=9.31 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.56 (bs, 1H), 8.93 (s, 2H), 8.37 (d, J=4.77 Hz, 1H), 7.25 (s, 1H), 4.63 (dd, J=10.67, 3.14 Hz, 1H), 4.47 (dd, J=10.79, 6.02 Hz, 1H), 3.81-3.89 (m, 4H), 1.83-1.91 (m, 2H), 1.72 (t, J=6.53 Hz, 1H), 1.08 (d, J=5.02 Hz, 6H).

Provenance & Evidence