N-(3-Aminopropyl)morpholine → HCID 59508063, compound

Participants

Reaction Steps

To a solution of 2-(2-methoxypyridin-3-yl)-1H-indole-5-carboxylic acid (0.850 g, 0.317 mmol) in dimethylformamide (5 ml) was added HBTU (1.20 g, 0.317 mmol) and N,N-diisopropylethylamine (0.70 ml, 0.519 g, 0.402 mmol). The reaction mixture was allowed to stir for five minutes and 3-morpholinopropan-1-amine (0.59 ml) was added. The reaction was allowed to stir for 2 hours at room temperature. The reaction was quenched by adding water (25 ml), saturated sodium bicarbonate solution (25 ml) and extracted with EtOAc (2×50 ml). The organic extracts were combined, washed with brine (1×25 ml), dried over sodium sulfate and concentrated. The crude product was purified by flash column chromatography (SiO2, 100% EtOAc to 3% MeOH in EtOAc) to give the desired product as a white solid (1.09 g, 87%). M.p.=224-225° C.; 400 MHz 1H NMR (DMSO-d6) δ: 11.55 (s, 1H), 8.36 (t, J=5.4 Hz, 1H), 8.23 (dd, J=1.6 Hz, 7.6 Hz, 1H), 8.17 (dd, J=2.0 Hz, 5.2 Hz, 1H), 8.11 (s, 1H), 7.65 (dd, J=2 Hz, 8.4 Hz, 1H), 7.47 (d, J=8.4, 1H), 7.18-7.12 (m, 2H), 4.06 (s, 3H), 3.60-3.56 (m, 4H), 3.35-3.27 (m, 2H), 2.38-2.31 (m, 6H), 1.76-1.66 (m, 2H); LCMS: 395 [M+H]. Hydrolysis as described in General Procedure O provides compound 55 in Table 2.

Provenance & Evidence