Cesium carbonate → HCID 86710355, compound

Participants

Reaction Conditions

Reaction Steps

An ambient temperature mixture of (S)-tert-butyl (1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-3-cyclopropylpropan-2-yl)carbamate (51 mg, 0.099 mmol), trimethylboroxine (0.015 mL, 0.109 mmol), PdCl2(dppf)-CH2Cl2 Adduct (8.06 mg, 9.88 μmol), cesium carbonate (64.4 mg, 0.198 mmol), 1,4-dioxane (1 mL), and water (0.33 mL) was charged to a pressure rated vial and purged with a stream of nitrogen for 10 minutes. The vial was sealed and stirred under nitrogen at 75° C. for 12 h. The resulting mixture was cooled to room temperature and vacuum filtered. The filtrate was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and brine. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The pooled organics were dried over magnesium sulfate, filtered, and concentrated to an oil. The oil was purified via silica gel chromatography (1% 2M ammonia in methanol/dichloromethane) to afford (S)-tert-butyl (1-cyclopropyl-3-((4,6,9-trimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (41 mg, 0.091 mmol, 92% yield) as a colorless oil. LC/MS, (ESI) m/z 452.3 [(M+H)+, calcd for C26H34N3O4 452.3]; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.59 (d, J=5.8 Hz, 1H), 7.90 (s, 1H), 7.78 (d, J=5.8 Hz, 1H), 6.74 (s, 1H), 4.91 (d, J=7.3 Hz, 1H), 4.35-4.04 (m, 3H), 3.71 (s, 3H), 3.14 (s, 3H), 2.31 (s, 3H), 1.72-1.59 (m, 2H), 1.48 (s, 9H), 0.86-0.70 (m, 1H), 0.60-0.44 (m, 2H), 0.21-0.00 (m, 2H).

Provenance & Evidence