Cesium carbonate → 2-[2-(2,6-Dichloro-4-cyano-phenyl)-thiazolo[5,4-c]pyridine-4-ylamino]-isonicotinonitrile

Participants

Reaction Conditions

Reaction Steps

Argon was bubbled through a suspension of 4-(4-bromo-thiazolo[5,4-c]pyridine-2-yl)-3,5-dichloro-benzonitrile (92 mg, 0.24 mmol), 2-amino-isonicotinonitrile (26 mg, 0.22 mmol), XantPhos (14 mg, 0.024 mmol) and cesium carbonate (195 mg, 0.6 mmol) in dioxane (2.5 ml) for 5 minutes then Pd2(dba)3 (11 mg, 0.012 mmol) was added. The reaction was heated at 70° C. for 8 hours and then cooled to room temperature. The reaction was partitioned between water (10 mL) and DCM (20 mL). The organic layer was separated, dried over Na2SO4 and concentrated to dryness under reduced pressure. The resultant residue was purified by silica gel flash chromatography eluting with 0-60% EtOAc in DCM. The resultant solid was triturated with diethyl ether, filtered, and left to air dry to give the desired compound as a yellow solid (64 mg, 63% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.74 (br s, 1H), 8.50 (dd, J=5.1, 0.9 Hz, 1H), 8.44 (d, J=5.6 Hz, 1H), 8.39 (s, 2H), 8.23 (s, 1H), 7.79 (d, J=5.6 Hz, 1H), 7.38 (dd, J=5.1, 1.4 Hz, 1H). LCMS (Method C): RT=4.70 min, m/z: 423 [M+H+].

Provenance & Evidence