Sodium Bicarbonate → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

A vial was charged with a mixture of 4-bromo-6-(trifluoromethyl)-1H-indazole (0.732 g, 2.76 mmol), (6-(methoxycarbonyl)pyridin-3-yl)boronic acid (0.5 g, 2.76 mmol) and PdCl2(dppf) (0.101 g, 0.138 mmol) in dioxane (10 mL) and aqueous saturated NaHCO3 (3 mL). The resulting light brown suspension was heated at 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated. The residue was diluted with DCM, washed with water, and the volatiles removed via rotary evaporation. The crude product was purified by CombiFlash® chromatography (0-30% MeOH in DCM over 180 minutes). The product-containing fractions were combined and concentrated by rotary evaporation to give product with some impurities (0.28 g). A portion of the product (20 mg) was re-purified by preparative HPLC, eluting with 40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes to give a TFA salt of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.95 (s, 3H), 7.69 (s, 1H), 8.07 (s, 1H), 8.23 (dd, J=8.21, 0.63 Hz, 1H), 8.39-8.57 (m, 2H), 9.10-9.26 (m, 1H), 13.86 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C15H10F3N3O2, 322.1. found 322.11.

Provenance & Evidence