Tributylphosphine → N-cyclopropyl-1-{4-[(ethylamino)carbonyl]phenyl}-5-{3-[4-(trifluoromethoxy)phenoxy]propyl}-1H-1,2,3-triazole-4-carboxamide

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Reaction Steps

To a solution of 4-(trifluoromethoxy)phenol (52 mg) in toluene (0.5 ml) was added a solution of tributylphosphine (51 mg) in toluene (0.5 ml) under stirring, a solution of N-cyclopropyl-1-{4-[(ethylamino)carbonyl]phenyl}-5-(3-hydroxypropyl)-1H-1,2,3-triazole-4-carboxamide (29 mg) in toluene (0.5 ml) and a solution of 1,1′-[(E)-diazene-1,2-diyldicarbonyl]dipiperidine in toluene (0.5 ml) were successively added, and the mixture was stirred at room temperature for 64 hr. The reaction mixture was filtered through a filter tube (Biospin column, Bio-Rad), and washed with 1 ml of ethyl acetate. The filtrates were combined, 1 ml of ethyl acetate and 1 ml of saturated aqueous sodium hydrogen carbonate solution were added, and the mixture was vigorously stirred at room temperature for 30 min. The organic layer was recovered using Presep™ Dehydration (Wako Pure Chemical Industries, Ltd.) and concentrated to dryness. The residue was dissolved in DMSO (0.7 ml) and purified by preparative HPLC (Gilson, Inc., high-throughput purification system, column: YMC CombiPrep ODS-A S-5 μm, 50×20 mm, solvent: solution A; 0.1% formic acid aqueous solution, solution B; 0.1% formic acid acetonitrile solution, gradient cycle: 0 min (solution A/solution B=95/5), 1.00 min (solution A/solution B=95/5), 5.20 min (solution A/solution B=5/95), 6.40 min (solution A/solution B=5/95), 6.50 min (solution A/solution B=95/5), 6.60 min (solution A/solution B=95/5), flow rate: 25 ml/min, detection method: UV 220 nm) to give the title compound (27 mg) (LC/MS purity 100%, ESI+:518 [M+H]+).

Provenance & Evidence