反应详情

A flask was charged with crude (2S,4R)—N-(4-(4-fluorophenoxy)phenyl)-4-hydroxypyrrolidine-2-carboxamide (0.452 g), 2-(1H-1,2,3-triazol-1-yl)acetic acid (169 g, 1.33 mmol), DIEA (3.0 mL, 17 mmol), HATU (0.506 g, 1.33 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature for 1 hour and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue was purified by reverse phase HPLC to provide Compound 75, (2S,4R)-1-(2-(1H-1,2,3-triazol-1-yl)acetyl)-4-(4-fluorobenzyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.115 g, 0.222 mmol, 23% yield). 1H-NMR (400 MHz, CDCl3): δ 8.95 (s, 1H), 7.77 (d, 2H), 7.43 (d, 2H), 7.16 (dd, 2H), 7.04-6.98 (m, 4H), 6.94-6.89 (m, 3H), 5.28 (d, 1H), 5.14 (d, 1H), 4.80 (d, 1H), 4.12 (dd, 1H), 3.68 (dd, 1H), 3.26 (t, 1H), 3.02-2.92 (m, 1H), 2.89 (dd, 1H), 2.71-2.59 (m, 1H), 2.74-2.65 (m, 1H). MS (EI) for C28H25F2N5O3 found 518.2 (MH+).

1. customquenched with saturated sodium bicarbonate (aq., 10 mL)
2. extractionThe mixture was extracted with ethyl acetate (20 mL)
3. washthe extract was washed with deionized water (10 mL)
4. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customProduct was purified from the residue
8. customwas purified by reverse phase HPLC