Potassium Carbonate → 2-[5-fluoro-2-(hydroxymethyl)-3-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]phenyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

Participants

Reaction Conditions

Reaction Steps

A microwave vial equipped with a magnetic stirrer was charged with 116c (300 mg, 0.78 mmol), 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 101k (545 mg, 1.13 mmol), potassium carbonate (414 mg, 3.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (68 mg, 0.075 mmol), tricyclohexyl phosphine (210 mg, 0.75 mmol), water (0.2 mL), and dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, the sealed vial was heated at 110° C. overnight. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 116 as a white solid (52 mg, 10%). MS-ESI: [M+H]+ 663.3. 1H NMR (500 MHz, DMSO) δ 8.23 (bs, 1H), 8.11 (s, 1H), 7.88 (d, J=4.5 Hz, 1H), 7.35-7.31 (m, 1H), 7.23-7.17 (m, 2H), 7.13-7.09 (m, 2H), 6.52 (s, 1H), 4.57-4.45 (m, overlap, 4H), 4.31 (d, J=7.5 Hz, 2H), 4.11-4.01 (m, 4H), 3.51-3.47 (m, 1H), 3.10-3.06 (m, 4H), 2.59-2.41 (m, 8H), 1.81-1.68 (m, 4H)

Provenance & Evidence