Water → N-[(1R)-2-Hydroxy-1-phenylethyl]-5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamide

Participants

Reaction Steps

To a solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxylic acid (Intermediate B, 250 mg, 1.08 mmol) in DMF (5 mL) was added O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (619 mg, 1.63 mmol), and the mixture was stirred at rt for 30 min. To this reaction mixture was then added (D)-(−)-2-phenylglycinol (198 mg, 2.17 mmol) in DMF (5 mL) followed by triethylamine (1.21 mL, 8.69 mmol), and the mixture was stirred at rt for 16 h. Water (10 mL) was added, and the mixture was extracted with ethyl acetate (1×25 mL), dried (Na2SO4), filtered, and concentrated to dryness. The crude material was purified with an ISCO CombiFlash Companion using gradient elution from 20% to 100% EtOAc in hexanes to afford the title compound as a white solid (370 mg, 97%): 1H NMR (300 MHz, DMSO-d6) δ 8.14 (d, 1H), 7.19-7.34 (m, 5H), 7.12 (d, 2H), 6.98 (d, 2H), 6.44 (s, 1H), 5.32 (s, 2H), 4.93-4.96 (m, 2H), 3.64-3.68 (m, 2H), 2.25 (s, 3H), 2.17 (s, 3H); ES-MS m/z 350.11, HPLC RT (Method B) 3.32 min.

Provenance & Evidence