Sodium Hydroxide → HCID 44177178, compound

Participants

Reaction Steps

To a N2 purged 100 mL round bottom flask attached with condenser was added 1-(3-Chloro-3′-methanesulfonyl-biphenyl-4-yl)-2-(2,6-dichloro-phenyl)-1H-imidazole-4-carboxylic acid (2-amino-2-methyl-propyl)-amide (590 mg, 1.00 mmol), POCl3 (0.91 mL, 10 mmol) and anhydrous 1,4-dioxane (35 mL). The reaction solution was heated at reflux for 2 hrs. The cooled reaction mixture was added H2O (50 mL) and the mixture as poured to a separatory funnel. To the mixture was added EtOAc (150 mL) and 1N aq. NaOH to raise the pH to 8. The aqueous phase was extracted with EtOAc (70 mL×2), and the combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and chromatographed through a 25 g SiO2 column using a gradient of 100% Hexane to 90% EtOAc to afford 288 mg (51% yield) of the title compound. MS (ESI) 573.3, 575.3, 577.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 9.07 (s, 1H), 8.23 (t, J=2 Hz, 1H), 8.21 (d, J=2 Hz, 1H), 8.11 (d, J=8 Hz, 1H), 7.96 (d, J=8 Hz, 1H), 7.86 (dd, J1=2 Hz, J2=8 Hz, 1H), 7.75 (t, J=8 Hz, 1H), 7.54-7.65 (m, 3H), 7.48 (d, J=8 Hz, 1H), 3.76 (s, 2H), 3.29 (s, 3H), 1.47 (s, 6H).

Provenance & Evidence