Hydrochloric Acid → HCID 54675149, 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) (80 mg, 0.137 mmol) and phenylboronic acid (24.97 mg, 0.205 mmol) in N,N-dimethylformamide (2.0 mL) was added saturated aqueous bicarbonate solution (683 μl) followed by bis(triphenylphosphine)palladium dichloride (6.71 mg, 9.56 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 a mixture of methanol (2 mL) and 2N aqueous sodium hydroxide solution (341 μl, 0.683 mmol) and heated by microwave irradiation (Biotage, Initiator) to 105° C. for 5 minutes. The reaction was cooled to room temperature, diluted with 1 mL DMSO, and acidified to pH ˜5 with 10% aqueous HCl solution. The sample 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 (300 MHz, DMSO-d6) δ 12.58 (bs, 1H), 8.34 (s, 1H), 8.26 (s, 1H), 8.01 (dd, J=7.1, 1.5 Hz, 2H), 7.53-7.43 (m, 2H), 7.43-7.34 (m, 1H), 7.07 (d, J=2.1 Hz, 1H), 6.66 (s, 1H), 2.70-2.57 (m, 2H), 2.46-2.34 (m, 2H), 2.07-1.89 (m, 2H); MS ESI(+) m/z 381.9 [M+H]+.

Provenance & Evidence