Bicarbonate Ion → HCID 54674065, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred ambient solution of 5-(6-iodo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(1-(methoxymethoxy)cyclobutyl)thiazole (Example 160C) (60 mg, 0.10 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (25.0 mg, 0.120 mmol) in N,N-dimethylformamide (2.0 mL) was added saturated aqueous bicarbonate solution (1.0 mL) followed by bis(triphenylphosphine)palladium dichloride (7.02 mg, 10.0 μmol). The mixture was heated to 70° C. for 3 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 (1 mL), and 4 molar aqueous HCl solution (0.5 mL) was added. The reaction was heated to 60° C. for 2 hours and was then cooled to room temperature. 4 Normal aqueous sodium hydroxide solution (1 mL) was added, and the reaction heated to 80° C. for 1 hour. The reaction was cooled to room temperature, and the pH adjusted to ˜7 with 10% aqueous HCl solution. The aqueous layer was extracted with ethyl acetate (3×). The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The solid was triturated with diethyl ether to give the title compound. 1H NMR (500 MHz, DMSO-d6) ppm 1.76-2.08 (m, 2H) 2.31-2.45 (m, 2H) 2.54-2.66 (m, 2H) 3.93 (s, 3H) 6.62 (s, 1H) 7.24 (s, 1H) 8.11 (s, 1H) 8.29 (s, 1H) 8.65 (s, 1H) 8.69 (s, 1H) 12.58 (s, 1H); MS ESI(+) m/z 353 (M+H)+.

Provenance & Evidence