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

Participants

Reaction Steps

To an 8 mL scintillation vial equipped for stirring was added (R)-3-methyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (80 mg, 0.293 mmol). DMF (0.5 mL), 3-cyano-3-methylazetidine (85 mg, 0.439 mmol), HOBt (67.2 mg, 0.439 mmol), EDC (84 mg, 0.439 mmol) and N,N-dimethylpyridin-4-amine (53.6 mg, 0.439 mmol) were added and the solution was stirred at 25° C. for 4 h. The fractions were collected and lyophilized to afford the title compound as a white solid (31.5 mg, 30.6%). 1H NMR (400 MHz, DMSO-d6) δ 0.78 (dd, J=6.82, 3.28 Hz, 3 H) 0.96 (dd, J=8.59, 6.32 Hz, 3 H) 1.44-1.68 (m, 3 H) 2.26-2.44 (m, 1 H) 3.84 (dd, J=9.47, 5.18 Hz, 1 H) 3.99-4.14 (m, 1 H) 4.21 (dd, J=9.47, 5.68 Hz, 1 H) 4.34-4.65 (m, 1 H) 4.85 (dd, J=19.45, 5.56 Hz, 1 H) 4.96-5.11 (m, 2 H) 7.08 (d, J=5.05 Hz, 1 H) 7.86 (d, J=4.04 Hz, 1 H) 8.26 (dd, J=4.80, 3.28 Hz, 1 H) 12.22 (br. s., 1 H). [M+H] calc'd for C19H21N5O2, 352; found, 352.5.

Provenance & Evidence