Cesium carbonate → HCID 178510056, compound

Participants

Reaction Steps

A partially purified product prepared in the manner described in Example 4A, step 5, except on a larger scale, was found to contain approximately 10 mol % 5-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]isophthalonitrile in addition to 3-chloro-5-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile. A solution of tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (Intermediate 1; 23 g, 74 mmol) in DMF (100 mL) was added to a suspension of the partially purified product (25 g, 82 mmol) and cesium carbonate (28 g, 86 mmol) in DMF (80 mL) at room temperature, and the resulting mixture was stirred for 1 hour at room temperature. The reaction mixture was then quenched with aqueous saturated ammonium chloride (200 mL), diluted with water (100 mL) and extracted with ethyl acetate (2×700 mL). The combined organic fractions were washed with dilute brine (3×500 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was adsorbed onto silica gel and subjected to automated silica gel chromatography eluting with a gradient of 25-50% ethyl acetate in hexanes to afford the crude title product. This mixture was then purified by reverse phase column chromatography eluting with 5-95% CH3CN/H2O (0.1% TFA) to yield the title compound. 1H NMR (DMSO-d6) δ 8.53 (dd, J=4.6 Hz, J=1.5 Hz, 1H), 8.22 (m, 1H), 8.15 (dd, J=8.2 Hz, J=1.5 Hz, 1H), 8.00 (m, 2H), 7.92 (d, J=8.9 Hz, 1H), 7.78 (d, J=8.9 Hz, 1H), 7.21 (dd, J=8.0 Hz, J=4.5 Hz, 1H), 6.39 (s, 2H). LRMS (M+1)=426.9.

Provenance & Evidence