反应详情

A solution of ethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)methylphosphinate (230 mg, 584 mmol) and 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (169 mg, 701 mmol) in TFE (2.0 mL) was charged with TFA (200 mg, 1.75 mmol) and the reaction mixture irradiated in a microwave reactor at 105° C. for 1 hour. The resulting mixture was concentrated under reduced pressure and the residue purified using an Isco Combiflash system eluting with 0→5% MeOH in DCM as eluent to afford the title compound, 337.5 mg (96.6% yield). 1H NMR (CDCl3, 400 MHz): δ=1.33 (t, J=6.95 Hz, 3 H), 1.45 (d, J=13.64 Hz, 3 H), 3.22 (s, 1 H), 3.24 (s, 3 H), 3.26 (s, 1 H), 4.03-4.15 (m, 2 H), 4.34 (s, 2 H), 7.36-7.41 (m, 2 H), 7.50 (d, J=8.08 Hz, 4 H), 7.54 (d, J=8.84 Hz, 1 H), 8.20 (s, 1 H), 8.30 (d, J=9.35 Hz, 1 H). MS (ES+): m/z 600.0844 [MH+] (TOF, polar).

1. customthe reaction mixture irradiated in a microwave reactor at 105° C. for 1 hour
2. concentrationThe resulting mixture was concentrated under reduced pressure
3. customthe residue purified
4. washeluting with 0→5% MeOH in DCM as eluent