2-Vinylpyridine → HCID 131724947, compound

Participants

Reaction Steps

N-Bromosuccinimide (254 mg, 1.42 mmol) was added to a stirred solution of 3-(5-methylisoxazol-3-yl)-6-(6-vinylpyridin-3-ylmethoxy)-[1,2,4]triazolo[3,4-α]phthalazine (500 mg, 1.30 mmol) in DMF (70 ml), H2O (10 ml) and AcOH (0.1 ml) and the resulting solution stirred at room temperature for 90 min and then 4 N NaOH (3 ml) was added. The mixture was concentrated under reduced pressure and then taken up in CH2Cl2 (100 ml), dried and concentrated. The mixture was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 as eluent to yield a 1:1 mixture of the vinylpyridine and the epoxide, m/z (ES+) 401 (M+H+), which was used without further purification. The crude residue was taken up in DMF (5 ml) in a sealed tube and azetidine (126 μl, 1.87 mmol) was added. The reaction was heated at 80° C. for 4 h. The reaction mixture was concentrated under reduced pressure and then taken up in MeOH/CH2Cl2, dry loaded onto silica and purified by column chromatography on silica using 8% MeOH/CH2Cl2 containing 1% NH3 as eluent. The fractions containing the correct compound were concentrated under reduced pressure and further purified on a prep. plate eluting with 7% MeOH/CH2Cl2 containing 1% NH3 to yield the desired phthalazine (4.9 mg, 1%). 1H NMR (400 MHz, CDCl3) δ 8.82 (1H, s), 8.64 (1H, d, J=7.4 Hz), 8.21 (1H, d, J=7.4 Hz), 8.06 (1H, d, J=7.4 Hz), 7.95 (1H, t, J=7.4 Hz), 7.80 (1H, t, J=7.4 Hz), 7.55 (1H, d, J=7.4 Hz), 6.84 (1H, s), 5.68 (2H, s), 4.68 (1H, dd, J=7.7, 3.5 Hz), 3.38-3.23 (4H, m). 2.87 (1H, dd, J=10.9, 3.5 Hz), 2.70 (1H, dd, J=10.9, 7.7 Hz), 2.60 (3H, s), 2.10 (2H, quintet, J=6.3 Hz). m/z (ES+) 457 (M+H+).

Provenance & Evidence