Sodium Carbonate → 5-(11-fluoro-6-(hydroxymethyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-methoxypyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of (S or R)-(2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methanol (35 mg, 0.115 mmol), 2-(6-methoxypyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (50 mg, 0.097 mmol) and sodium carbonate (20 mg, 0.188 mmol) in 2 mL of 1,4-dioxane and 0.2 mL of water was added Pd2(dba)3 (10 mg) and X-Phos (10 mg) under nitrogen. The reaction mixture was heated at 70° C. for 16 hours and concentrated in vacuo to remove 1,4-dioxane. And then the residue was suspended in water and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by prep-HPLC to give the product of (S or R)-5-(11-fluoro-6-(hydroxymethyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-methoxypyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, yield: 47%). 1H-NMR (CDCl3, 400 MHz) δ 8.72 (d, J=2.4 Hz, 1H), 8.14˜8.17 (m, 1H), 7.99 (s, 1H), 7.64 (s, 1H), 7.43˜7.48 (m, 2H), 7.14˜7.23 (m, 3H), 6.81˜6.86 (m, 2H), 6.42˜6.45 (m, 1H), 6.06 (brs, 1H), 4.01 (s, 3H), 3.98˜4.00 (m, 1H), 3.85˜3.88 (m, 1H), 3.37 (s, 3H), 2.96 (d, J=4.8 Hz, 3H), 2.72 (s, 3H), 2.27 (s, 1H). MS (M+H)+: 658.

Provenance & Evidence