1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-(4-fluorophenyl)pyrrolidin-2-one

Participants

Reaction Steps

To a suspension of 2-(3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.053 g, 0.223 mmol; Example 216A) and 5-fluoroisoindoline hydrogen chloride (0.043 g, 0.246 mmol) in dichloromethane (0.4 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.059 mL, 0.335 mmol) and the reaction stirred for 18 hours. The reaction was loaded onto a GraceResolv™ 12 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.34-7.16 (m, 4H), 7.08-6.93 (m, 3H), 4.82 (dd, J=8.6, 16.1, 4H), 4.27 (d, J=16.2, 1H), 4.15 (d, J=16.2, 1H), 3.79-3.59 (m, 3H), 2.67-2.51 (m, 1H), 2.18 (ddd, J=8.5, 12.9, 16.1, 1H); MS (ESI+) m/z 357.0 (M+H)+.

Provenance & Evidence