HCID 12665370, compound → Urea

Participants

Reaction Steps

3-Ethynlaniline (0.15 mL, 1.43 mmol) was added to a 20% solution of phosgene in toluene (4.04 mmol) followed by DIPEA (0.50 mL, 2.71 mmol). The reaction mixture was stirred at room temperature for 3 h. To this was added 3-aminomethyl-N-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-benzamide (250 mg, 0.69 mmol) and 1 mL of DMSO. The reaction mixture was stirred overnight at room temperature, then diluted with EtOAc (100 mL), washed with water (2×100 mL), dried with Na2SO4 and concentrated to provide 300 mg of a yellow solid. LC-MS indicated this was a mixture of primarily desired product and the symmetrical urea of ethynyl aniline. This material was triturated with methanol which enriched the ppt in desired product (now approximately 40%) and removed the residual amine. This solid was then partitioned between ethyl acetate and 2 N HCl. The aqueous phase was separated, neutralized, and extracted with ethyl acetate to provide a mixture ˜9:1 of the desired product and urea (25 mg yellow solid). This material was further purified by prep HPLC to provide 3 mg of 3-[3-(3-ethynyl-phenyl)-ureidomethyl]-N-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-benzamide. MS, electrospray, 447 (M+H).

Provenance & Evidence