Cesium carbonate → (Rac)-cis-3-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)cyclohexanol

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Reaction Conditions

Reaction Steps

A mixture of (rac)-cis-3-(2-fluoropyridin-3-yl)cyclohexanol (250 mg, 1.281 mmol), 4-(pyridin-2-ylamino)phenol (477 mg, 2.56 mmol), and cesium carbonate (834 mg, 2.56 mmol) in NMP (4 ml) was heated in a Biotage™ microwave reactor at 180° C. for 1.5 h. The mixture was partitioned between H2O (15 ml) and CH2Cl2 (30 ml), the layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×30 ml). The combined organic layers were dried (MgSO4), concentrated under reduced pressure, and the resulting brown oil was purified by reversed phase HPLC (Gilson Gemini-NX 10u C18 110A, 100×50.0 mm, 10% to 95% H2O/MeCN, 0.1% TFA). The product containing fractions were combined, neutralized by the addition of solid Na2CO3, and extracted with CH2Cl2 (3×20 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to deliver (rac)-cis-3-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)cyclohexanol as a tan solid. MS (ESI, pos. ion) m/z: 362.0 (M+1). IC50 (uM) 0.011024.

Provenance & Evidence