Cesium carbonate → HCID 178484153, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of intermediate 6, cis-3-{[(tert-butoxycarbonyl)(methyl)-amino]methyl}cyclobutyl methanesulfonate (2 g, 6.9 mmol), intermediate 21, 3,5-difluoro-4-(pyrrolidin-1-ylmethyl)phenol (3.47 g, 13.8 mmol) and Cs2CO3 (4.5 g, 13.8 mmol) in DMSO (20 mL) was heated at 90-95° C. for 4 h under vigorous stirring in a flow of argon, then cooled. Water (40 ml) and EtOAc (40 ml) were added, and the layers were separated. The water layer was extracted with ether (20 ml), the combined organic layers were washed with 1N NaOH (3×25 mL), brine, dried with Na2SO4, and evaporated to give the title compound (2.8 g, 98%) as a yellow oil. LC/MS data: 411.6, 412.6 (M+H) (calculated for C22H32F2N2O3 410.51). 1H NMR-data (DMSO-d6): 6.50-6.61 (m, 2H, Ar—H); 4.79-4.87 (m, 1H); 3.55 (s, 2H, CH2); 3.32 (d, 2H, J=8.1 Hz, CH2); 2.78 (s, 3H, NCH3); 2.52-2.62 (m, 1H); 2.38-2.50 (m, 4H); 2.20-2.28 (m, 2H); 2.05-2.17 (m, 2H); 1.58-1.73 (m, 4H); 1.41 (s, 9H, Boc).

Provenance & Evidence