N,N,N',N'-Tetramethylazodicarboxamide → 2-[3-(4-Morpholinyl)phenoxy]ethyl 3-(1-piperazinyl)-2-pyrazinyl ether

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Reaction Steps

1,1′-Azobis(N,N-dimethylformamide) (TMAD; 256 mg, 1.50 mmol) was added to a solution of 2-[3-(4-tert-butoxycarbonyl-1-piperazinyl)-2-pyrazinyloxy]ethanol (400 mg, 1.24 mmol; prepared in Example 52, Step 2), 3-(4-morpholinyl)phenol (441 mg, 1.23 mmol) and triphenylphosphine (646 mg, 2.46 mmol) in THF (3 mL). The reaction mixture was stirred at room temperature for 2.5 h and then concentrated. The residue was purified by repeated chromatography on silica gel using toluene and toluene/EtOAc (8:2) as eluents. Solvents were evaporated and the residue was treated with CH2Cl2/TFA/H2O (1:0.9:0.1; 5 mL) at room temperature for 0.5 h After concentration 5 M NaOH was added followed by extraction with CH2Cl2. The organic phase was dried (K2CO3), filtered, and concentrated. The residue was purified by chromatography on silica gel using CHCl3/MeOH (9:1) as eluent to give 50 mg (10%) of the title product as on oil. HRMS m/z calcd for C20H27N5O3(M)+385.2114, found 385.2100.

Provenance & Evidence