Sodium Carbonate → 5-(2-(4-methylpiperazin-1-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with N-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide (Intermediate II, 0.200 g, 0.353 mmol), 1-(2-bromo-5-(trifluoromethyl)phenyl)-4-methylpiperazine (Intermediate JJ, 0.228 g, 0.706 mmol), and PdCl2(dppf)-CH2Cl2 adduct (0.058 g, 0.071 mmol). Dioxane (1.765 ml) and t-BuOH (1.765 ml) were added, followed by sodium carbonate (2.0M in H2O) (0.530 ml, 1.059 mmol). The reaction was purged with nitrogen, and then heated at 50° C. overnight. After cooling to RT, the solids were filtered through a frit and washed with ethyl acetate. The filtrate was then washed with brine, and the organics were dried over magnesium sulfate, filtered and concentrated to yield a dark oil. Before deprotection, the material was dissolved in methanol and purified further with a strong cation exchange-column (SCX) (product eluted with the methanol/ammonia wash). After concentration, the material was diluted with DCM (1.0 mL) and TFA was added (1.0 mL). The reaction was stirred for 30 minutes at which time the reaction was concentrated under a vacuum. The material was purified via reverse-phase preparative HPLC using 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min to provide 5-(2-(4-methylpiperazin-1-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate (0.064 g, 0.099 mmol, 28.0% yield) as a tan glass. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.98-2.17 (m, 1H) 2.23-2.42 (m, 1H) 2.76-2.95 (m, 2H) 3.00-3.15 (m, 4H) 3.17 (s, 3H) 6.85 (d, J=4.60 Hz, 1H) 7.27 (d, J=4.60 Hz, 1H) 7.45-7.57 (m, 3H) 7.65-7.82 (m, 4H) 8.25 (d, J=7.63 Hz, 1H) 8.55 (d, J=1.86 Hz, 1H) 9.61 (br. s., 1H) 12.81 (br. s., 1H). m/z (ESI) 533.0 (M+H)+.

Provenance & Evidence