Acetonitrile--water (1/1) → HCID 178511589, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (725 mg, 2.185 mmol) was added DMSO (7 ml), trans-cyclohexane-1,4-diamine (1996 mg, 17.48 mmol) and TEA (0.609 ml, 4.37 mmol) was stirred at about 100° C. for 20 hours. The reaction was monitored by LC/MS. The crude reaction mixture mixture was cooled to room temperature, diluted with 3 ml DMSO, filtered, and purified by prep HPLC. (there is a general HPLC conditions in the general experimental session). The fractions were concentrated, mixed with 500 ml ethyl acetate, and basified with saturated sodium bicarbonate 120 ml. The ethyl acetate layer was separated, and the basic water layer was extracted with 300 ml ethyl acetate. The ethyl acetate layers were combined and washed with water (3×), saturated salt solution (1×), dried with sodium sulfate, filtered and concentrated to yield a solid. The solid was dissolved in (1:1 ACN/water) filtered and lyapholized to yield 755 mg of the title compound as free-base. LCMS (m/z): 426.3 (MH+), retention time=0.59 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.10-1.43 (m, 4 H) 1.90 (d, J=12.01 Hz, 2 H) 2.01 (d, J=12.01 Hz, 2 H) 2.70-2.84 (m, 1 H) 3.47-3.60 (m, 1 H) 4.48 (s, 2 H) 6.44 (d, J=8.50 Hz, 1 H) 6.51 (s, 1 H) 6.71 (d, J=7.33 Hz, 1 H) 6.79-6.91 (m, 1 H) 7.00 (d, J=9.96 Hz, 1 H) 7.05-7.13 (m, 1 H) 7.15-7.27 (m, 1 H) 7.40 (t, J=7.77 Hz, 1 H) 7.85 (s, 1 H)

Provenance & Evidence