Sodium Iodide → 9-(4-(2,2-difluoroethoxy)phenyl)-N-(4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-fluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine 2,2,2-trifluoroacetate

Participants

Reaction Steps

A solution of 5-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(4-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-fluorophenyl)-1H-1,2,4-triazol-3-amine (787 mg, 1.47 mmol), sodium iodide (1.10 g, 7.37 mmol), and diisopropylethylamine (1.29 mL, 7.37 mmol) in acetone (30 mL) was heated in a sealed vessel at 100° C. for 3 h. The reaction was concentrated in vacuo. After an aqueous workup, the crude organic concentrate was purified using reverse phase preparatory HPLC (MeOH/water/TFA) to afford 145 mg (16% yield) of the titled compound as the TFA salt. LC-MS (M+H)+ 498.3. 1H NMR (500 MHz, CHLOROFORM-d) d ppm 9.45 (1 H, br. s.), 7.69 (1 H, dd, J=12.5, 2.1 Hz), 7.29 (1H, t, J=8.5 Hz), 7.18 (1 H, d, J=8.5 Hz), 7.04 (2 H, d, J=8.5 Hz), 6.93 (2 H, d, J=8.5 Hz), 6.08 (1 H, tt, J=55.1, 4.1 Hz), 4.40 (1 H, d, J=7.9 Hz), 4.30-4.37 (1 H, m), 4.21-4.30 (1 H, m), 4.17 (2 H, td, J=13.0, 4.1 Hz), 2.45 (3H, s), 2.42 (3 H, s), 2.25-2.35 (1 H, m), 2.06-2.17 (1 H, m), 1.84-2.04 (4 H, m).

Provenance & Evidence