Cesium carbonate → HCID 87222480, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-methoxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate [2-(ethylcarbamoylamino)-7-[(E)-N-methoxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]trifluoromethanesulfonate (220 mg, 0.5 mmol), bis-(neopentyl glycolato)diboron (226 mg, 1 mmol) and potassium acetate (147 mg, 1.5 mmol) were weighed into a Kymax tube. DMF (4 mL) was added and the mixture degassed by bubbling N2 through for 15 min. Pd(dppf)Cl2 (26 mg, 0.05 mmol) was added and the reaction sealed and heated to 80° C. for 3 h at the end of which time LCMS indicated clean boronate formation. The reaction was allowed to cool to ambient temperature then divided into 2 aliquots in reaction tubes. To one of the tubes was added 1-(5-Bromo-pyrimidin-2-yl)-4-ethyl-piperidine-4-carboxylic acid ethyl ester (103 mg, 0.3 mmol), cesium carbonate solution (170 μl, 0.63 mmol, 3.7M aq. soln.) and Pd(dppf)Cl2 (13 mg, 0.025 mmol) were added and the reaction sealed and heated to 90° C. for 3 h at the end of which time LCMS indicated formation of the desired product. The reaction mixture was diluted with EtOAc, washed with water then brine and the organic layer dried (MgSO4), filtered and the solvent was removed in vacuo. The crude material obtained was purified by flash chromatography on silica gel using a gradient of petrol-EtOAc 0-100% as the eluent to give the desired compound as an off white solid, 87 mg, 32% yield.

Provenance & Evidence