Cesium carbonate → HCID 59508073, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 3-bromo-2-(2-methoxypyridin-3-yl)-5-(3-morpholinopropylcarbamoyl)-1H-indole-1-carboxylate (0.38 mmol), phenylboronic acid (69 mg, 0.57 mmol), Cs2CO3 (0.18 g, 0.57 mmol) in dioxane (3 ml) and water (1 ml) was added Pd(PPh3)4 (43 mg, 0.038 mmol). The reaction mixture was heated at 100° C. for up to 3 h. The reaction mixture was quenched by adding ethyl acetate (15 ml) and saturated NaHCO3 (10 ml). The ethyl acetate layer was separated and washed with brine (10 ml), dried with Na2SO4, filtered and concentrated to give a crude product. The crude product was purified using flash column chromatography (SiO2, 5% EtOAc in hexanes to 10% EtOAc in hexanes). The desired product, tert-butyl 2-(2-methoxypyridin-3-yl)-5-(3-morpholinopropylcarbamoyl)-3-phenyl-1H-indole-1-carboxylate was obtained as a light yellow solid (0.017 g, 47%); 400 MHz 1H NMR (DMSO-d6) δ: 8.57 (t, J=5.2 Hz, 1H), 8.24 (d, J=8.8 Hz, 1H), 8.17 (dd, J=1.2 Hz, 4.4 Hz, 1H), 8.10-7.98 (m, 1H), 7.92 (dd, J=1.2 Hz, 8.4 Hz, 1H), 7.45 (dd, J=1.6 Hz, 7.6 Hz, 1H), 7.40-7.23 (m, 3H), 7.23-7.19 (m, 1H), 6.94-6.89 (m, 1H), 3.87 (s, 3H), 3.57-3.50 (m, 4H), 3.34-3.25 (m, 2H), 2.35-2.28 (m, 6H), 1.71-1.62 (m, 2H), 1.24 (s, 9H); LCMS: 571 [M+H]. Hydrolysis as described in example 33 provides compound 1 in Table 2.

Provenance & Evidence