Dichloromethane → 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (30.0 mg, 59.7 μmol), 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine (from Alfa Aesar, cat# H51659, 19.8 mg, 6.57 μmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloro-methane (1:1) (4.9 mg, 5.97 μmol), and potassium phosphate (25.4 mg, 119 μmol) in water (0.2 mL)/1,4-dioxane (1 mL) was heated at 88° C. After 1 hour, the volatiles were removed under vacuum and the residue was dissolved in methanol (1 mL). Potassium carbonate (16.5 mg, 119 μmol) was added and the reaction mixture was warmed up to 60° C. After 1 hour, the reaction mixture was cooled to ambient temperature and was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (10.1 mg, 44%) as its (trifluoroacetic acid) TFA salt. LCMS calculated for C27H32N5O2 (M+H)+: m/z=458.2. Found: 458.2; 1H NMR (400 MHz, DMSO-d6): δ 12.21 (s, 1H), 9.73 (s, 1H), 8.01 (s, 1H), 7.89 (d, J=9.2 Hz, 2H), 7.12 (d, J=9.2 Hz, 2H), 6.93 (d, J=2.0 Hz, 1H), 6.38 (d, J=2.4 Hz, 2H), 6.28 (t, J=2.4 Hz, 1H), 4.01 (d, J=14.0 Hz, 2H), 3.67 (s, 6H), 3.52 (d, J=12.8 Hz, 2H), 3.19-2.93 (m, 8H), 2.86 (d, J=4.0 Hz, 3H) ppm.

Provenance & Evidence