Potassium Phosphate, Tribasic → 5-(3-Chloro-2-fluoro-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-2-(2-methoxy-phenyl)-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

Participants

Reaction Conditions

Reaction Steps

A degassed mixture of 2-bromo-5-(3-chloro-2-fluoro-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Intermediate A) (0.392 mmol), 2-methoxyphenylboronic acid [5720-06-9] (0.549 mmol), (Ph3P)2PdCl2 (0.039 mmol) and K3PO4 (1.569 mmol) in DMF (4 mL) was heated at 100° C. for 8 h. After cooling to rt, the reaction mixture was concentrated. The residue was diluted with a saturated aqueous solution of NaHCO3 and extracted with EtOAc (3×). The combined organic phases were successively washed with water and brine, dried (Na2SO4) and concentrated. The residue was dissolved in MeOH and filtered through a PL-thiol MP SPE cartridge (StratoSpheres), washing through with additional MeOH. The filtrate was re-concentrated and the residue purified using a RediSep® silica gel column to afford the title compound as a light yellow solid. tR: 8.55 min (HPLC 2); ESI-MS: tR=1.43 min, [M+H]+523/525 (LC-MS 1); TLC: Rf=0.41 (98:2 CH2Cl2/MeOH); 1H-NMR (d6-DMSO, 600 MHz): (rotamers) 7.56 (d, 0.5H), 7.50-7.56 (m, 1.5H), 7.45-7.49 (m, 1.5H), 7.30 (d, 1H), 7.27 (m, 1H), 7.19-7.25 (m, 2H), 7.14 (d, 1H), 7.05 (m, 1H), 6.92 (d, 0.5H), 6.51/6.67 (s, 1H), 6.25/6.27 (s, 1H), 3.93/3.97 (m, 1H), 3.77 (s, 3H), 1.87/2.36 (s, 3H), 1.27 (m, 3H), 0.48 (m, 3H).

Provenance & Evidence