1,1'-Carbonyldiimidazole → HCID 10287424, compound

Participants

Reaction Steps

The title compound was prepared from reaction of the product of Example 5, Step B, 3,4-difluoro-2-[[2-fluoro-4-(3-methoxy-1-propynyl)phenyl]-amino]benzoic acid. This product (200 mg, 0.60 mmol) was dissolved in dry THF (5 mL) and CDI (193 mg, 1.19 mmol) added. After 0.5 hours at room temperature, TLC showed complete conversion to the desired imidazolide. A solution of 2-(aminooxy)ethanol (184 mg, 2.39 mmol) in dry THF (2 mL) was added and the reaction mixture stirred overnight at room temperature. The reaction solvent was then removed under reduced pressure and the resulting residue partitioned between EtOAc (50 mL) and saturated NaHCO3 solution (50 mL). The EtOAc layer was then dried (Na2SO4), the solvent removed under reduced pressure, and the resulting oil purified by column chromatography on silica gel (50% EtOAc/hexanes) to give 3,4-difluoro-2-[[2-fluoro-4-(3-methoxy-1-propynyl)phenyl]amino]-N-(2-hydroxyethoxy)benzamide as a white solid (165 mg, 71%); mp (EtOAc/Et2O) 121-123° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.84 (br s, 1 H), 8.85 (br s, 1 H), 7.46-7.38 (m, 1 H), 7.32 (dd, J=12.1, 1.7 Hz, 1 H), 7.29-7.21 (m, 1 H), 7.14 (dd, J=8.4, 1.6 Hz, 1 H), 6.79 (td, J=8.8, 4.7 Hz, 1 H), 4.74 (br s, 1 H), 4.30 (s, 2 H), 3.84 (t, J=4.8 Hz, 2 H), 3.56 (t, J=4.9 Hz, 2 H), 3.32 (s, 3 H). Anal. Calcd for C19H17F3N2O4: C, 57.9; H, 4.4; N, 7.1. Found C, 57.9; H, 4.3; N, 7.0.

Provenance & Evidence