Citric Acid → HCID 18404005, compound

Participants

Reaction Steps

A suspension of acid washed zinc dust (0.12 g, 1.80 mmol) and 1,2-dibromoethane (0.015 ml, 10 mol %) in dry DMF (3 ml) was stirred at room temperature under nitrogen for 5 min then warmed to 40° C. A solution of neopentyl iodide (0.25 ml, 1.85 mmol) in dry DMF (1 ml) was added and the mixture was stirred at 40° C. for 3 h. A solution of 3-(2-fluorophenyl)-5-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-6-bromo-1,2,3-triazolo[4,5-b]pyridine (0.15 g, 0.37 mmol) (Example 3, step c), tris(dibenzylideneacetone)dipalladium(0) (0.008 g, 2.5 mol %) and tri-2-furylphosphine (0.017 g, 20 mol %) in dry DMF (2 ml) was stirred at 40° C. under nitrogen for 10 min followed by addition of the organozinc reagent via syringe. The mixture was stirred for 18 h at 40° C. then cooled, diluted with water (60 ml), acidified with 1M aqueous citric acid and extracted with dichloromethane (2×30 ml). The extracts were dried (Na2SO4), filtered and concentrated. Preparative thin layer chromatography on silica gel, eluting with 2% methanol-dichloromethane, and trituration of the product with diethyl ether gave 3-(2-fluorophenyl)-5-(2-methyl-2H-1,2,4triazol-3-ylmethoxy)-6-(2,2-dimethylpropyl)-1,2,3-triazolo[4,5-b]pyridine (0.060 g, 41%) as a white solid, m.p. 130-133° C. Found: C, 60.03; H, 5.51; N, 24.37. C20H22N7OF.0.25(H2O) requires C, 60.06; H, 5.67; N, 24.52%. δH (360 MHz; CDCl3) 0.93 (9H, s), 2.68 (2H, s), 3.82 (3H, s),5.52 (2H, s), 7.36-7.42 (2H, m), 7.54-7.61 (1H, m), 7.69 (1H, dd, J=7 and 7), 7.86 (1H, s) and 8.10 (1H, s); m/z (ES+) 396 (M+H+).

Provenance & Evidence