Cesium carbonate → 3,5-Dichloro-4-[4-(6-ethylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-benzonitrile

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Reaction Conditions

Reaction Steps

A mixture of 4-(4-bromothiazolo[5,4-c]pyridin-2-yl)-3,5-dichlorobenzonitrile (0.095 g, 0.25 mmol), 6-ethylpyrimidin-4-ylamine (29 mg, 0.23 mmol), Pd2(dba)3 (11 mg, 0.012 mmol), XantPhos (14 mg, 0.025 mmol) and cesium carbonate (0.201 g, 0.62 mmol) in dioxane (2.5 mL) was degassed with a stream of nitrogen. The reaction mixture was heated at 70° C. for 16 hours. After cooling to room temperature, the resultant mixture was diluted with water and filtered through Celite® washing with DCM. The aqueous phase was further extracted with DCM and the combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resultant residue was purified by silica gel flash C18 column chromatography eluting with 0-100% EtOAc in pentane followed by a 20-60% gradient MeOH in H2O+1M HCl (1.25 mL in each 25 mL of eluent). The product containing fractions were combined and concentrated under reduced pressure. The resultant solid was suspended in a mixture DCM/EtOAc/MeOH and washed with a saturated solution of NaHCO3, then dried and concentrated under reduced pressure. Further column chromatography purification on silica gel, eluting with 0-50% EtOAc in DCM, afforded the title compound as a pale yellow solid (30 mg, 28% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.70 (br s, 1H), 8.66 (d, J=1.2 Hz, 1H), 8.46 (d, J=5.6 Hz, 1H), 8.39 (s, 2H); 7.84 (d, J=5.6 Hz, 1H), 7.56 (s, 1H), 2.67 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). LCMS (Method C): RT=3.81 min, m/z: 427 [M+H+].

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