tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 6-bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole (360 mg, 0.831 mmol), tert-butyl piperazine-1-carboxylate (387 mg, 2.077 mmol), sodium tert-butoxide (319 mg, 3.32 mmol) and BINAP (10.4 mg, 0.017 mmol) in toluene (5.5 mL) was added Pd2(dba)3 (45.6 mg, 0.050 mmol). Upon completion of addition, the reaction mixture was stirred in a sealed vial at 80° C. overnight. At the conclusion of this period, the reaction mixture was cooled to rt, diluted with water and then extracted with EtOAc (3×5 mL). The combined organic layers were washed with saturated NaHCO3 (5 mL) and brine (5 mL), dried (Na2SO4), filtered, and then concentrated to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc) to afford Compound 12A as a white solid (248 mg, 0.460 mmol, 55% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 8.18 (2H, s), 7.54-7.61 (1H, m), 7.15-7.23 (1H, m), 6.99-7.07 (1H, m), 5.37-5.44 (1H, m), 4.17-4.27 (2H, m), 3.65-3.77 (2H, m), 3.55-3.65 (4H, m), 3.06-3.18 (4H, m), 2.42 (2H, t, J=7.6 Hz), 2.13-2.22 (2H, m), 1.89-2.00 (2H, m), 1.56-1.64 (2H, m), 1.50 (9H, s), 0.95 (3H, t, J=7.3 Hz). LC/MS (m/z)=539 (M+H)+.

Provenance & Evidence