Diethyl Ether → Ethyl 1-[5-[7-cyclohexyl-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Participants

Reaction Steps

Cyclohexylmagnesium chloride in Et2O (2.03 mL, 3.65 mmol) was added to a THF (2.5 mL) solution of LiCl (53 mg, 1.25 mmol) and 1M zinc chloride in Et2O (4.38 mL, 4.38 mmol) at rt, after which a grey precipitate immediately formed. After stirring at rt for 15 mins, a THF solution (3 mL) of 1-{5-[7-Bromo-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester (100 mg, 182.66 mmol) and Pd(dppf)Cl2.DCM (10 mol %) and was allowed to stir at rt for 30 mins. Subsequent heating at reflux gave minimal formation of the desired product and an equimolar amount of the hydrodebrominated starting material. The reaction mixture was transferred to a microwave vessel and heated at 110° C. for 30 mins. The reaction mixture was quenched with 1M HCl (1×5 mL), extracted with EtOAc (10 mL), dried (MgSO4), concentrated in vacuo and subjected to reverse phase HPLC (60-80% water (0.1% FA):MeOH) to afford 2.7 mg (3% isolated yield) of a white solid.

Provenance & Evidence