Cesium carbonate → 5-Chloro-2-(2,3-dimethoxypropoxy)-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)nicotinonitrile

Into a 50-mL 3-neck-bottle purged and maintained with an inert atmosphere of nitrogen were placed a solution of 5,6-dichloro-2-(2,3-dimethoxypropoxy)nicotinonitrile (1.40 g, 4.59 mmol, 1.00 equiv, 95%) in DMSO (20 mL), benzo[c][1,2]oxaborole-1,5(3H)-diol (800 mg, 5.07 mmol, 1.10 equiv, 95%) and Cs2CO3 (1.88 g, 5.78 mmol, 1.20 equiv). The resulting solution was stirred for 2 h at 50° C. in an oil bath. The reaction mixture was then cooled and quenched by the addition of 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate. The organic layers were combined, dried and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with EtOAc/petroleum ether (1:5). This resulted in 1.09 g (57%) of 5-chloro-2-(2,3-dimethoxypropoxy)-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)nicotinonitrile as a white solid. LC-MS (ES, m/z): 405 [M+H]+. 1H-NMR (300 MHz, DMSO-d6) δ (ppm) 9.27 (1H, m); 8.61 (1H, m); 7.82 (1H, d, J=8.1 Hz); 7.34 (1H, m); 7.26 (1H, m); 5.00 (2H, s); 4.12-4.17 (1H, m); 3.97-4.03 (1H, m); 3.25-3.30 (1H, m); 3.17 (6H, s).

1. customInto a 50-mL 3-neck-bottle purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. temperatureThe reaction mixture was then cooled
4. customquenched by the addition of 20 mL of water
5. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
6. customdried
7. concentrationconcentrated under vacuum
8. washeluted with EtOAc/petroleum ether (1:5)
9. customThis resulted in 1.09 g (57%) of 5-chloro-2-(2,3-dimethoxypropoxy)-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)nicotinonitrile as a white solid

ORD 기록

ord-b7f1a41a77444f8eb28e05927f5a36c5

출처 데이터셋

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08716478B2