反应详情

Methyl-(2S)-2-[(3,5-dichloroisonicotinoyl)amino]-3-[2-(2,6-dichlorophenyl)-6-quinolinyl]propanoate (410 mg, 0.75 mmol) was dissolved in THF (2 ml) and added drop wise over 3 hrs to a stirred aqueous solution of NaOH (2 M, 2.5 ml). After addition was complete the reaction was stirred at RT for 1 hour, before the THF was removed in vacuo. The resulting slurry was diluted with water (6 ml) and acidified to pH-4 using HCl (12 M). The resultant precipitate was collected by filtration, washed with water (15 ml) and dried overnight in vacuo (40° C.) to yield the desired product as a white powder (274 mg, 68%). LCMS M+1 (535, 537), M−1 (534, 536) Retention Time 3.39 min, 1H NMR, 300 Mz, d6-DMSO-13.00 (1H, brs), 9.40 (1H, d), 8.65 (2H, s), 8.42 (1H, d), 7.98 (1H, d), 7.94 (1H, d), 7.78 (1H, dd), 7.65 (2H, d), 7.54 (2H, m), 4.90 (1H, m), 3.45 (1H, brs), 3.20 (1H, dd). Chiral HPLC 97% ee Retention time 6.29 min (Column-CHIRALPAK AD 250*4.6 mm, 10 m; Solvent A 1-Propanol+0.1% TFA, Solvent B Isohexane; Isocratic 20% A: 80% B; Temperature 40° C.; Run Time 15 min; Detection 280 nM).

1. additionAfter addition
2. customwas removed in vacuo
3. additionThe resulting slurry was diluted with water (6 ml)
4. filtrationThe resultant precipitate was collected by filtration
5. washwashed with water (15 ml)
6. customdried overnight in vacuo (40° C.)