Phthalimide → 2-((3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methyl)isoindoline-1,3-dione

Participants

Reaction Steps

To a suspension of (3-chloropyrazin-2-yl)-(2-phenylquinolin-7-yl)-methanol (1.215 g, 3.49 mmol), phthalimide (566 mg, 3.85 mmol), and PS—PPh3 (loading 2.12 mmol/g; 3.29 g, 6.97 mmol) in dry THF (40 mL), cooled by ice/water, is added DIAD (830 μL, 852 mg, 4.22 mmol). The cooling bath is removed and the flask is vortexed at rt for Id. More phthalimide (50 mg, 0.34 mmol), PS—PPh3 (300 mg, 0.636 mmol), and DIAD (80 μL, 82 mg, 0.41 mmol) are added, and vortexing is continued for 2 d. The resin is filtered off on a glass frit (porosity M) and washed with CH2Cl2. The combined filtrates and washings are concentrated in vacuo and chromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with CH2Cl2 (1-22)→2% EtOAc in CH2Cl2 (23-38)→5% (39-61)], mixed fractions are combined and chromatographed again [50 g/150 mL cartridge, eluting with CH2Cl2 (1-22)→2% EtOAc in CH2Cl2 (23-33)→3% (34-55)→5% (56-68)] to obtain the title compound as white foam. 1H NMR (CDCl3, 400 MHz) δ 7.14 (s, 1H), 7.43-7.55 (m, 3H), 7.72-7.79 (m, 3H), 7.82-7.90 (m, 4H), 8.09 (s, 1H), 8.09-8.14 (m, 2H), 8.22 (d, J=8.8 Hz, 1H), 8.40 (d, J=2.4 Hz, 1H), 8.51 (d, J=2.4 Hz, 1H). MS (ES+): m/z 476.9/478.9 (100/38) [MH+]. HPLC: tR=3.5 min (MicromassZQ, nonpolar—5 min).

Provenance & Evidence