Phthalimide → HCID 59852832, compound

Participants

Reaction Conditions

Reaction Steps

To a solution/suspension of {3-[8-amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-phenyl}-methanol (312 mg, 0.737 mmol), isoindole-1,3-dione (130 mg, 0.885 mmol), and PS-PPh3 (loading 2.12 mmol/g; 696 mg, 1.47 mmol) in anhydrous THF (15 mL), cooled to 0° C., DIAD (218 μL, 224 mg, 1.11 mmol) was added dropwise, under N2 atmosphere. After 10 min, the cooling bath was removed and the reaction mixture stirred at ambient temperature for 3d. The resin was filtered off on a glass frit (porosity M) and washed with large volumes of THF and then CH2Cl2. The filtrate was concentrated, adsorbed onto Hydromatrix, and the crude material (0.6843 g) was purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with MeOH:CH2Cl2 0.5%→3%], yielding the title compound as a yellow solid. Sample contains ≈0.3 eq. of reduced DIAD by 1H NMR; 1H NMR (CDCl3, 400 MHz) δ 4.94 (s, 2H), 5.07 (s, 2H), 5.16 (s, 2H), 7.07 (ddd, J=8.4, 2.8, 1.2 Hz, 1H), 7.11 (d, J=5.2 Hz, 1H), 7.28-7.33 (m, 3H), 7.33-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.43-7.47 (m, 2H), 7.50 (t, J=7.6 Hz, 1H), 7.53-7.56 (m, 1H), 7.62 (d, J=5.2 Hz, 1H), 7.72 (dd, J=5.6, 2.8 Hz, 2H), 7.74-7.77 (m, 1H), 7.86 (dd, J=5.2, 3.2 Hz, 2H), 7.92 (s, 1H); MS (ES+): m/z 552.3 (100) [MH+].

Provenance & Evidence