Cesium carbonate → HCID 117737381, compound

Participants

Reaction Conditions

Reaction Steps

A 5-mL vial was sequentially charged with 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (300 mg, 0.642 mmol), cesium carbonate (154 μl, 1.926 mmol), dimethyl sulfoxide (2.1 mL), and (hydroxymethyl)cyclopropane (130 μL, 1.605 mmol). The vial was sealed with a PTFE lined cap and heated to 90° C. After 16 h, the brown reaction mixture was allowed to cool to RT, then diluted with IPA (3 mL) and filtered through a pad of celite. The pad was rinsed with IPA (2×5 mL) and the filtrate was concentrated under reduced pressure to furnish a brown oil, which was dissolved in DMSO (2 mL) filtered through a 0.2 micron filter and purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 20 to 75% MeCN in water (containing 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min to afford 1-(5-chloro-6-(cyclopropylmethoxy)-2-methoxy-3-pyridinyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (180 mg, 0.358 mmol, 55.7% yield) as a tan amorphous solid. 1H NMR (500 MHz, DMSO-d6) δ=11.65 (br. s., 1H) 8.72 (s, 1 H) 8.36 (s, 1 H) 8.21 (d, J=9.67 Hz, 1 H) 8.04 (s, 1 H) 7.85 (dd, J=8.95, 1.75 Hz, 1 H) 7.00 (d, J=9.02 Hz, 1 H) 6.79 (d, J=9.67 Hz, 1 H) 6.45 (d, J=1.10 Hz, 1 H) 4.23-4.40 (m, 2 H) 3.78 (s, 3 H) 1.30-1.43 (m, 1 H) 0.62 (d, J=7.66 Hz, 2 H) 0.41 (br. s., 2 H). m/z (ESI) 503.3 (M+H)+.

Provenance & Evidence