Bicarbonate Ion → HCID 54672778, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred ambient solution of 1-(5-(5-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 8A) (50 mg, 0.085 mmol) and 3-cyanophenylboronic acid (18.8 mg, 0.128 mmol) in N,N-dimethylformamide (2.0 mL) was added saturated aqueous bicarbonate solution (683 μl) followed by bis(triphenylphosphine)palladium dichloride (4.2 mg, 6.0 μmol). The mixture was heated to 70° C. for 4 hours and was then quenched by the addition of water and ethyl acetate. The layers were separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in methanol (2 mL). Magnesium turnings (20.7 mg, 0.853 mmol) and solid ammonium chloride (18.26 mg, 0.341 mmol) were added, and the mixture stirred vigorously for 16 hours. The reaction was partitioned between ethyl acetate and saturated aqueous bicarbonate solution. The layers were separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD m column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid). The fractions containing the product were diluted with ethyl acetate and washed with saturated aqueous bicarbonate solution. The ethyl acetate solution was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the title compound. 1H NMR (500 MHz, DMSO-d6) δ 12.71 (s, 1H), 8.57 (bs, 1H), 8.39 (s, 1H), 8.35 (d, J=8.4 Hz, 1H), 8.30 (s, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.70-7.67 (m, 1H), 7.35 (bs, 1H), 6.70 (s, 2H), 2.68-2.59 (m, 2H), 2.46-2.38 (m, 2H), 2.06-1.89 (m, 2H); MS ESI(+) m/z 406.9 [M+H]+.

Provenance & Evidence