Hydrochloric Acid → [4-(7-Amino-6-pyridin-4-yl-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl)-cyclohexyl]-acetic acid

Participants

Reaction Conditions

Reaction Steps

4-Pyridine boronic acid (0.156 mmol, 20 mg), K2CO3 (0.234 mmol, 33 mg), and Pd(PPh3)4 (0.008 mmol, 10 mg) was added to a solution of (4-{7-[bis-(2-trimethylsilanyl-ethoxymethyl)-amino]-6-bromo-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-5-yl}-cyclohexyl)-acetic acid ethyl ester (0.078 mmol, 60 mg) in dioxane (1 mL). To this suspension was added distilled H2O (0.2 mL). The resulting reaction mixture was stirred at 100° C. under argon for 18 hours. The reaction mixture was concentrated in vacuo. The crude mixture was dissolved in 2:1 MeOH:H2O (1.5 mL) and was treated with 2N NaOH(aq) (0.5 mL). The resulting reaction mixture was stirred at room temperature for 18 hours. Aqueous hydrochloride solution (1.0 N, 2 ml) was added to the reaction mixture and the resulting solution was stirred at 65° C. for 2 h. The solution was concentrated in vacuo and purified by prep-LC to afford the title compound (3.6 mg) as a mixture of cis and trans isomers: LC/MS RT=2.84 min. Mass calculated for, M+H 479.21, observed 479.21.

Provenance & Evidence