Pyridine → HCID 178458726, compound

Participants

Reaction Conditions

Reaction Steps

3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid (2.03 g, 6.61 mmol) was dissolved in DCM (33 mL) with DMF (0.05 mL), and cooled to 0° C. Oxalyl chloride (1.16 mL, 13.22 mmol) was added dropwise and the mixture was allowed to stir for 1.5 hours. The reaction mixture was concentrated under reduced pressure to remove residual oxalyl chloride. The yellow oil was re-dissolved in DCM (33 mL), and 5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (1.71 g, 7.17 mmol) and pyridine (0.86 mL, 10.5 mmol) were added. After 16 hours, the reaction mixture was concentrated under reduced pressure and partitioned in EtOAc (50 mL) and water (50 mL). The organic layer was rinsed with water (30 mL), and then a saturated sodium chloride solution (30 mL), dried over sodium sulfate, filtered, and concentrated to brown oil. After chromatography on silica gel with a gradient from 5-30% ethyl acetate-hexanes, N-[5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-yl]-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide (1.25 g, 36.0% yield) was obtained. 1H NMR (300 MHz, DMSO-d6): δ 10.65 (s, 1H), 8.25 (s, 1H), 8.05 (d, J=6.0 Hz, 1H), 7.65 (d, J=6.0 Hz, 1H), 7.40 (d, J=3.0 Hz, 1H), 7.25 (s, 1H), 7.15 (s, 1H), 7.10 (s, 1H), 7.05 (d, J=3.0 Hz, 1H), 6.60 (s, 1H), 4.65 (s, 2H), 4.60 (m, 1H), 4.15 (t, 2H), 2.95 (t, 2H), 1.05 (s, 3H), 1.0 (s, 3H), 0.85 (s, 9H), 0.00 (s, 6H); LCMS (m/z): 527.3 [C28H38N2O4SSi+H]+.

Provenance & Evidence