Cesium carbonate → HCID 86710446, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 8-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (1.26 g, 4.88 mmol), prepared as in Example 16, Part G, (S)-tert-butyl (5,5-difluoro-1-hydroxypent-4-en-2-yl)carbamate (1.39 g, 5.86 mmol), 2-di-t-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.42 g, 0.98 mmol), Pd(OAc)2 (0.11 g, 0.49 mmol), Cs2CO3 (3.18 g, 9.76 mmol), and anhydrous toluene (15 mL) was purged with nitrogen for 10 minutes and heated to 90° C. overnight (15 h). After cooling, the reaction mixture was filtered through diatomaceous earth (Celite®), concentrated under reduced pressure and dissolved in ethyl acetate (50 mL). The organic layer was washed with brine (1×100 mL) and water (1×100 mL); dried over Na2SO4 and concentrated under reduced pressure to afford an amber oil. The crude material was purified over SiO2 (1-5% 2M ammonia in methanol/dichloromethane gradient elution) to afford (S)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-5,5-difluoropent-4-en-2-yl)carbamate (1.04 g, 2.26 mmol, 46% yield) as a tan solid. LC/MS, (ESI) m/z 460.0 [(M+H)+, calcd for C24H28F2N3O4, 460.2]; 1H NMR (400 MHz, CDCl3) δ ppm 8.59 (d, J=5.5 Hz, 1H), 8.05 (d, J=8.8 Hz, 1H), 7.73 (d, J=5.8 Hz, 1H), 6.83 (dd, J=8.8, 1.8 Hz, 1H), 6.79 (br. s., 1H), 5.13-4.89 (m, 1H), 4.39-4.21 (m, 1H), 4.20-3.96 (m, 3H), 3.66 (s, 3H), 3.12 (s, 3H), 2.61-2.31 (m, 2H), 1.48 (s, 9H).

Provenance & Evidence