Triethylamine → HCID 178502881, compound

Participants

Reaction Steps

To a solution of (S)-1-((S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methoxypropan-1-one (Example 5, Steps A-C, 52.1 mg, 0.106 mmol) and cyanogen bromide (13.4 mg, 0.127 mmol) in dichloromethane (1 mL) was slowly added triethylamine (35.3 mg, 0.349 mmol). After stirring for 20 minutes at room temperature, the mixture was concentrated under reduced pressure and dissolved in ethanol (2 mL). To this solution was added methoxyamine hydrochloride (600 mg, 7.18 mmol) and triethylamine (642 mg, 6.35 mmol). The reaction vessel was sealed and heated to 70° C. for 24 hours. The mixture was concentrated under reduced pressure and dissolved in ethyl acetate. The precipitate was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was chromatographed (3% 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 white solid (7.3 mg, 13% yield). MS APCI (+) m/z 492 (M+1) detected; 1H NMR (400 MHz, CD3OD) δ 7.65-7.60 (m, 1H), 7.47-7.45 (m, 2H), 7.42-7.37 (m, 2H), 7.35-7.29 (m, 3H), 4.79 (q, 1H, J=7.0 Hz), 3.73 (s, 3H), 3.45-3.37 (m, 2H), 3.36 (s, 3H), 3.28-3.19 (m, 1H), 2.60-2.51 (m, 1H), 2.19-2.08 (m, 1H), 1.71-1.60 (m, 1H), 1.43 (d, 3H, J=7.0 Hz).

Provenance & Evidence