Methylurea → HCID 86677206, compound

Participants

Reaction Conditions

Reaction Steps

A 500 mL 3-neck RBF was equipped with magnetic stirrer, heating mantle, set-point controller, thermowell, thermocouple and nitrogen bubbler. The flask was charged with 3-(2-chloro-3-fluorobenzyl)-1-(S)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-hydroxypropan-2-yl)-1-methylurea (15.7 g, 41.9 mmol), iodobenzene diacetate (27 g, 2.0 equiv.) and methyl tert-butyl ether (141 mL). The mixture was warmed to ˜55° C. and the amide (7.6 g, 1.05 equiv.) was added in small portions. The reaction was stirred for 1 h. The reaction was cooled to ambient temperature and quenched by addition of saturated aq. NaHCO3 (150 mL). The organic phase was extracted with ethyl acetate, and the combined organics were washed with water and brine. The organic phase was dried over MgSO4 and concentrated. Residual solvents were removed by azeotrope from DCM and hexanes (3×) to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(R)-2,2-dimethyl-1,3-dioxolan-4-yl)propyl isoquinolin-3-ylcarbamate as a solid (25.3 g), which was used without further purification. LRMS (M+H+) m/z 545.1.

Provenance & Evidence