1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-(3-Chloromethyl-[1,2,4]oxadiazol-5-yl)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

Participants

Reaction Conditions

Reaction Steps

7-Methyl-1-oxo-2-(4-trifluoromethoxybenzyl)-2,3-dihydro-1H-isoindole-5-carboxylic acid (80.0 mg, 0.49 mmol), EDCI (104.0 mg, 0.54 mmol), HOBT (73.0 mg, 0.54 mmol) and 2-chloro-N-hydroxyacetamidine (59.0 mg, 0.54 mmol) were mixed in DMF (4.0 mL) over the weekend. The reaction mixture was diluted with EtOAc and washed with water, brine, dried over sodium sulfate, filtered and concentrated. The product was subjected to column chromatography (100% EtOAc). The product was heated to 135° C. in DMF for 1.5 hours. The reaction mixture was cooled and diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate, filtered and concentrated. The product was purified by column chromatography to yield the title compound as a brown oil (63.0 mg, 33%). 1H NMR (300 MHz, CDCl3): δ 8.01 (d, 2H), 7.37 (d, 2H), 7.21 (d, 2H), 4.81 (s, 2H), 4.69 (s, 2H), 4.34 (s, 2H), 2.85 (s, 3H).

Provenance & Evidence