1,2-Dichloroethane → (2R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methyl-N-(tetrahydrofuran-3-yl)butanamide

Participants

Reaction Steps

To an 8 mL scintillation vial equipped for stirring was added (R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (15 mg, 0.051 mmol). DMF (0.5 mL), tetrahydrofuran-3-amine (0.077, 6.7 mg), HOBt (11.83 mg, 0.077 mmol), EDC (14.81 mg, 0.077 mmol) and N,N-dimethylpyridin-4-amine (9.44 mg, 0.077 mmol) were added and the solution was stirred at 25° C. for 4 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%). The fractions were collected and lyophilized to afford the title compound as a white solid (7.3 mg, 39.3%). 1H NMR (400 MHz, CD3OD) δ 0.93 (d, J=6.57 Hz, 3 H) 1.04 (dd, J=6.57, 2.78 Hz, 3 H) 1.74-1.95 (m, 1 H) 2.21 (d, J=7.83 Hz, 1 H) 2.42-2.54 (m, 1 H) 3.50-3.67 (m, 1 H) 3.69-3.97 (m, 3 H) 4.37 (td, J=3.85, 1.89 Hz, 1 H) 4.96-5.12 (m, 2 H) 5.36-5.52 (m, 1 H) 7.86 (s, 1 H) 8.17 (d, J=3.28 Hz, 1 H). [M+H] calc'd for C18H21FN4O3, 361; found, 361.4.

Provenance & Evidence