Hydrochloric Acid → HCID 86639134, compound

Participants

Reaction Steps

To cooled (0° C.) solution of 3-(5-(2,5-difluorophenyl)-3-((S)-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)propanenitrile (0.052 g, 0.13 mmol, Example 14, Step C) in ethanol (0.5 mL) was added 9.8 M ethanolic HCl (0.5 mL, 4.9 mmol). After stirring at room temperature for 6 hours, the mixture was concentrated under reduced pressure. To the residue was added methoxylamine hydrochloride (0.021 g, 0.21 mmol), absolute ethanol (0.5 mL) and triethylamine (0.087 mL, 0.63 mmol). After stirring at room temperature for 16 hours, the mixture was concentrated under reduced pressure. The residue was diluted with 10% Na2CO3 (30 mL) and extracted with dichloromethane. The combined organics were dried, filtered and concentrated under reduced pressure. The residue was chromatographed (40% ethyl acetate in hexanes) to afford the product as a mixture of diastereomers (14 mg, 25% yield). MS ESI (+) m/z 463 (M+1) detected; 1H NMR (4001 MHz, CDCl3) δ 7.50 (m, 2H), 7.38 (m, 8H), 7.30 (m, 2H), 7.13 (m, 4H), 4.78 (q, 1H, J=6.3 Hz), 4.72 (q, 1H, J=6.3 Hz), 4.64 (br. s, 4H), 3.77 (s, 6H), 3.54 (m, 2H), 3.41 (s, 3H), 3.36 (s, 3H), 2.68 (m, 4H), 2.18 (m, 2H), 1.51 (d, 3H, J=6.3 Hz), 1.49 (d, 3H, J=7.0 Hz).

Provenance & Evidence