2-Fluoroethyl bromide → 4-(2,3-Difluorobenzylamino)-6-(4-(1-(2-fluoroethyl)piperidin-4-yl)phenylamino)nicotinamide

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Reaction Steps

Compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (85 mg, 0.18 mmol) was dissolved in 3 mL NMP with DIEA (95 μL, 0.54 mmol). To it was added 1-bromo-2-fluoroethane (230 mg, 1.8 mmol). The mixture was stirred at RT for overnight. The reaction was about 70% completion. It was quenched with TFA and concentrated in vacuo. The mixture was subjected to reverse phase preparative HPLC to isolate the title compound (53 mg). MS found for C26H28F3N5O as (M+H)+ 484.4. UV: λ=256 nm. 1H NMR: (CD3OD) δ 8.19 (1H, s), 7.37 (2H, d, J=8.4 Hz), 7.25 (1H, m), 7.19-7.14 (3H, m), 7.10 (1H, m), 5.82 (1H, s), 4.97 (1H, m), 4.85 (1H, m), 4.55 (2H, s), 3.77 (2H, d, J=12.0 Hz), 3.62 (1H, m), 3.55 (1H, m), 3.28 (2H, m), 3.00 (1H, m), 2.15 (4H, m) ppm.

Provenance & Evidence