Cesium carbonate → 2,6-dichloro-N-(2-isobutyramidopyridin-4-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

To a 10 ml microwave tube was added N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (60 mg, 0.21 mmol), followed by 2-methylpropanamide (43 mg, 0.5 mmol), cesium carbonate (162 mg, 0.5 mmol), Pd2(dba)3 (15 mg, 0.016 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 11 mg, 0.02 mmol). The tube was degassed and filled with N2 three times. The resulting mixture was then heated 100° C. overnight. The next day, the mixture was cooled to room temperature, filtered through celite. The filtrate was concentrated to dryness and the resulting thick oil was dissolved in EtOAc (10 mL), and washed with H2O (10 mL). The aqueous layer was further extracted with EtOAc (10 mL). Combined organics were dried over Na2SO4, concentrated and purified by reverse-phase HPLC (Gemini, 3×10 cm, gradient: 5-85% CH3CN/H2O with 0.1% NH4OH over 10 min) to afford the desired product (30 mg, 49% yield). 1HNMR: (DMSO-d6, 400 MHz): δ 11.2 (s, 1H), 10.4 (s, 1H), 8.4 (s, 1H), 8.2 (d, J=5.2 Hz, 1H), 7.60-7.46 (m, 4H), 2.74 (m, 1H), 1.1 (d, J=6.8 Hz, 6H). LCMS (ESI) (m/z): 352.0 [M+H+].

Provenance & Evidence