Triethylamine → HCID 178502877, compound

Participants

Reaction Conditions

Reaction Steps

Preparation of 1-(2-(2,5-difluorophenyl)-3-((S)-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)ethyl)-2-methoxyguanidine hydrochloride: To a solution of crude (2-(5-(2,5-difluorophenyl)-3-((S)-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)ethyl)cyanamide (31 mg, 0.072 mmol) and methoxyamine hydrochloride (151 mg, 1.80 mol) in ethanol (3 mL) was added triethylamine (182 mg, 1.80 mmol). After heating to 70° C. in a sealed vessel for 16 hours, additional methoxyamine hydrochloride (151 mg, 1.80 mol) and triethylamine (182 mg, 1.80 mmol) was added, and the reaction mixture was heated to 70° C. in a sealed vessel for an additional 24 hours. The mixture was cooled to room temperature and diluted with ethyl acetate. The salts were removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was chromatographed (4% methanol in dichloromethane with 0.5% NH4OH), and the isolated material was treated with excess HCl in MeOH then concentrated to afford the product as a mixture of diastereomers (23 mg, 62% yield). MS APCI (+) m/z 478 (M+1) detected; 1H NMR (400 MHz, CD3OD) δ 7.69-7.64 (m, 2H), 7.50-7.38 (m, 8H), 7.37-7.29 (m, 6H), 4.83-4.78 (m, 2H), 3.80-3.67 (m, 2H), 3.73 (s, 6H), 3.54-3.45 (m, 2H), 3.45-3.33 (m, 2H), 3.39 (s, 3H), 3.31 (s, 3H), 3.04-2.92 (m, 2H), 1.49 (d, 3H, J=7.1 Hz), 1.45 (d, 3H, J=7.1 Hz).

Provenance & Evidence