Sodium Carbonate → tert-butyl 4-{4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]phenyl}piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of tert-butyl 4-[4-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl]piperazine-1-carboxylate (4 mg, 1.25 mmol), 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-Indazole (1.04 g, 1.87 mmol), and tetrakis(triphenylphosphine)palladium(0) (144 mg, 0.13 mmol) in degassed DME (5.5 mL) was added aqueous Na2CO3 solution (2 M, 1.87 mL). The reaction was heated (80° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL). The layers were separated and the aqueous phase was back extracted with ethyl acetate. The combined organics were washed with brine, dried (Na2SO4), and concentrated to dryness. The crude material was purified by ISCO® chromatography using a gradient of 25 to 75% ethyl acetate in hexanes to afford 378 mg (58%) of the desired product, which contained trace impurities. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (s, 1 H), 7.88 (s, 1 H), 7.78 (d, 1 H), 7.57 (s, 1 H), 7.36-7.31 (m, 5 H), 7.13 (d, 1 H), 6.61 (s, 1 H), 5.64 (s, 2 H), 4.13-3.98 (m, 2 H), 3.35-3.25 (m, 1 H), 2.05-1.96 (m, 2 H), 1.63-1.50 (m, 2 H), 1.41 (s, 9 H); ES-MS m/z 524.2 [M+H]+, HPLC RT (min) 3.08.

Provenance & Evidence