Methylamine → 2-[2-(3,5-dimethoxyphenyl)ethyl]-N-methyl-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Steps

To a stirred solution of crude 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5-{[2-(trimethylsilyl)ethoxy]methyl}-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (20 mg, 31.6 μmol) in N,N-dimethylformamide (2 mL), HATU (12.0 mg, 31.6 μmol), 2.0 M methylamine in THF (15.8 μL, 31.6 μmol) and N,N-diisopropylethylamine (11.0 μL, 63.3 mmol) were added sequentially at ambient temperature. After 1 hour, the reaction was quenched with saturated aqueous NH4Cl, extracted with methylene chloride. The combined organic layers were dried over MgSO4, concentrated. The residue was dissolved in methylene chloride (1 mL) and trifluoroacetic acid (1 mL) was added at ambient temperature. After 2 hours, the volatiles were removed under vacuum and the residue was dissolved in methanol (1 mL), followed by the addition of ethylenediamine (0.1 mL). After another 1 hour, the reaction mixture 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 (3.5 mg) as its TFA salt. LCMS calculated for C29H35N6O3 (M+H)+: m/z=515.3. Found: 515.2.

Provenance & Evidence