Cesium fluoride → 2-hydroxy-N,N-dimethyl-2-{5-[3-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-pyridin-3-yl}-acetamide

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Reaction Steps

A mixture of 2-hydroxy-2-{5-[3-iodo-1(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-N,N-dimethyl-acetamide (194 mg, 0.4 mmol), 1-methyl-5(tributylstannyl)3-(trifluoromethyl)-1H-pyrazole (186 mg, 0.4 mmol), CuI (7 mg, 0.04 mmol), CsF (107 mg, 0.7 mmol), dichlorobis(benzonitrile)palladium (II) (7 mg, 0.02 mmol), tri-t-butylphosphine 10% w/v in hexanes (10 μl, 0.04 mmol) and DMF were stirred at 100° C. under nitrogen overnight. The mixture was allowed to cool to room temperature and then extracted with ethyl acetate (2X). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. The material was purified using silica gel chromatography and a gradient of ethyl acetate and hexane. The purified product was treated with dichloromethane/trifluoroacetate acid (1 ml/1 ml) at room temperature for 2 hours. The solvents were removed under vacuum and the crude was stirred in dichloromethane/ethylenediamine (1 ml/1 ml) for 2 hours at room temperature. Again the solvents was removed under vacuum and the crude was dissolved in DMSO, filtered and purified by reverse phase HPLC, lyophilized afforded 2-hydroxy-N,N-dimethyl-2-{5-[3-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-pyridin-3-yl}-acetamide (13.2 mg, 8% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.80 (s, 3H), 2.94 (s, 3H), 5.56 (s, 1H), 5.80 (s, 1H), 7.08 (s, 1H), 7.98 (s, 1H), 8.04 (t, 1H), 8.26 (d, 1H), 8.50 (d, 1H), 8.58 (d, 1H), 8.88 (d, 1H), 12.40 (s, 1H). MS: m/z 445.0 (M+H+).

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