Triethylamine → 4-(1-(4-methoxybenzyl)-3-vinyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (2.45 g, 5.00 mmol; prepared as in Example 7, Step B), potassium vinyltrifluoroborate (0.804 g, 6.00 mmol), triethylamine (0.693 mL, 5.00 mmol), and n-propanol (20 mL) was sparged with N2 for 5 minutes, and then Pd(dppf)Cl2 (82 mg, 0.10 mmol) was added. The sealed reaction was heated at 10° C. for 2 hours. The product and residual starting material were separated from catalyst and other by-products and re-subjected to the reaction conditions as follows. The reaction was concentrated in vacuo. The residue was partitioned between DCM (30 mL) and water (30 mL). The phases were separated, and the aqueous phase was re-extracted with DCM (2×10 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was separated from catalyst and other by-products by Biotage Flash 40, eluting with 20% EtOAc/hexanes then 1:1 EtOAc/hexanes. The product and starting material (1:1 ratio by 1H NMR) was resubjected to the same reaction conditions as above. After 2 hours at 100° C., all starting material had been consumed. After workup and Biotage Flash 40 purification as before, the product was obtained as an off-white solid (1.29 g, 66%). 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J=6 Hz, 1H), 7.33 (d, J=9 Hz, 2H), 7.18 (m, 1H), 7.01 (t, J=9 Hz, 1H), 6.82 (d, J=9 Hz, 2H), 6.52 (m, 2H), 6.34 (m, 1H), 6.23 (m 1H), 5.62 (s, 2H), 5.45 (m, 1H), 3.81 (br s, 2H), 3.76 (s, 3H).

Provenance & Evidence