Nitrogen → HCID 67520656, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB8) (60 mg, 0.127 mmol, 1 eq), 2-chloro-7-fluoro-4-trifluoromethyl-1,3-benzothiazole (42 mg, 0.153 mmol, 1.2 eq), and potassium carbonate (43 mg, 0.317 mmol, 2.5 eq) in 20% aq. dioxane (15 mL) was bubbledN2 gas for 15 min. Catalyst PdCl2dppf (5 mol %) was added to the stirred solution and N2 gas bubbling continued for another 10 min. The reaction mixture was then heated at 80° C. for 2 h. Cooling of the reaction mixture and evaporation of dioxane under reduced pressure yielded a brown residue. It was diluted with water (50 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield a yellowish-green solid. It was purified by column chromatography (50% ethyl acetate in hexane) to afford the BOC-protected title compound as yellowish-green solid; MS(ES+): m/z=563 [MH+]. To a solution of this Boc derivative (40 mg, 0.07 mmol) at 0-5° C. in dry DCM (10 ml) was added 4M HCl in dioxane (0.2 ml) dropwise and stirred the reaction mixture overnight at rt. Removed solvent under reduced pressure to afford the title compound as yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=9.06-8.96 (brm, 1H), 8.85-8.73 (brm, 1H), 8.61 (d, J=2.0 Hz, 1H), 8.42 (s, 1H), 8.41 (d, J=2.0 Hz, 1H), 8.17 (very brs, 1H), 8.09 (s, 1H), 8.03 (dd, J=5.2, 8.4 Hz, 1H), 7.59 (t, J=8.4 Hz, 1H), 4.56-4.46 (mc, 1H), 3.41 (brd, J=12.4 Hz, 2H), 3.12 (brq, J=11.4 Hz, 2H), 2.31-2.11 (m, 4H). MS(ES+): m/z=463.05 (100) [MH+], 380.02 (80) [MH+-piperidine]. HPLC: tR=2.29 min (polar—5 min, ZQ2).

Provenance & Evidence