Diisopropylethylamine → 1-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-3-oct-2-enylpyrrolidine-2,5-dione

Participants

Reaction Steps

O-Benzotriazol-1-yl-N,N,N′N′-tetramethyluronium tetrafluoroborate (0.107 g, 0.33 mmol) and diisopropylethylamine (0.098 ml, 0.56 mmol) were added sequentially at ambient temperature to a stirred solution of 2-{[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]methyl}-dec-4-enoic acid (0.123 g, 0.26 mmol) in dimethylformamide (2 ml), the mixture was stirred at ambient temperature for 48 hours, then it was added dropwise to ice-cold water (10 ml). The product was extracted into ethyl acetate (2×5 ml), the extracts were combined, dried (MgSO4) and the solvent was removed in vacuo. The residue was triturated with hexane (3 ml) and the resulting solid was collected by filtration and dried in vacuo to give 1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-3-oct-2-enylpyrrolidine-2,5-dione (0.055 g) as an off-white solid, m.pt 138–141° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 0.7–0.9 (m, 3H) (CH3), 1.1–1.4 (m, 6H) (—CH2CH2CH2CH3) 1.9–2.1 (m, 2H) (—CH2-nBu), 2.3–2.6 (m, 1H+2H) (—CHCH2CH═CH—), 2.8–3.2 (m, 2H) (ring CH2), 4.4 (s, 2H) (ArCH2—), 5.25–5.45 and 5.45–5.7 (2×m, 2×1H) (—CH═CH—) 7.2–7.3 (m, 1H)(ArH), 7.3–7.5 (m, 1H) (ArH), 7.5–7.6 (m, 1H) (ArH), 7.8–8.05 (m, 3H)(3×ArH), 8.3 (d, 1H) (ArH), 12.65 (s, 1H) (CONH); m/z (M+H)+. 462, 90% purity.

Provenance & Evidence