Dichloromethane → Ethyl 1-[5-[7-bromo-2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

1-(5,7-Dibromo-6-methoxy-1,3-benzothiazol-2-yl)-3-ethyl-urea (Intermediate 14) (234 mg, 0.57 mmol), ethyl 4-methyl-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]piperidine-4-carboxylate (716 mg, 1.14 mmol, 60 mass %) and PdCl2(dppf).DCM (23 mg, 0.03 mmol) were dissolved in dioxane (7.5 mL) in a 10-20 mL microwave vial and a solution of cesium carbonate (559 mg, 1.72 mmol) in water (2.5 mL) was added. The vial was capped, the mixture degassed and heated in the microwave at 110° C. for 30 minutes. The mixture was poured into water and extracted into EtOAc (4×40 mL). The organic layers were washed with brine, dried over Na2SO4 and concentrated to dryness in vacuo. The mixture was purified by chromatography, Biotage SP4, 40 g Si cartridge, 10-100% EtOAc in heptane. Two compounds were detected with the same mass ion (m/z) and retention time by LCMS but were distinct by TLC (60% EtOAc in heptane) so were assumed to be two regioisomers. The relevant fractions were combined to give the desired compound as a pale yellow oil, 47 mg (14%). MS: 577.04/579.07 [M+H]+.

Provenance & Evidence