4-Methylmorpholine → (R)-1-(3,3-dimethyl-2-(6-methyl-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoyl)azetidine-3-carbonitrile

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Reaction Steps

(R)-3,3-Dimethyl-2-(6-methyl-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (10 mg, 0.033 mmol), DMAP (6 mg, 0.05 mmol), 4-methylmorpholine (0.015 mL, 0.13 mmol), EDC hydrochloride (10 mg, 0.050 mmol), HOBt hydrate (8 mg, 0.050 mmol) and azetidine-3-carbonitrile hydrochloride (6 mg, 0.050 mmol) were dissolved in DMF (2 mL). The reaction mixture was stirred under nitrogen at room temperature for 3 h. The solution was concentrated and purified by preparative HPLC (10-30% AcCN/H2O with 0.035% TFA) to give the title compound (1.4 mg, 12%). 1H NMR (500 MHz, CD3OD) δ 1.18 (s, 9H), 2.35 (d, J=8.8 Hz, 3H) 4.17-4.18 (m, 1 H), 4.29-4.31 (m, 2 H), 4.52-4.62 (m, 1 H), 4.64-4.69 (m, 1 H), 5.19-5.23 (m, 2 H), 5.45 (s, 1 H), 7.83 (d, J=16.1 Hz, 3 H), 8.19 (s, 1 H). [M+H] calc'd for C20H23N5O2, 366; found, 366

Provenance & Evidence