Sodium Iodide → N-(3-{1-[(3S)-3-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-YL)-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide

Participants

Reaction Conditions

Reaction Steps

A mixture of potassium carbonate (29.2 mg, 0.211 mmol), sodium iodide (47.5 mg, 0.317 mmol), 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (51.8 mg, 0.211 mmol) and 2-[(1S)-3-chloro-1-phenylpropyl]-1H-isoindole-1,3(2H)-dione (63.1 mg, 0.211 mmol) in DMF (5.0 mL) was stirred at 100° C. for 3 hrs, at which time TLC indicated that the reaction was complete. The reaction mixture was cooled to room temperature, poured into water (50 mL) and the aqueous layer was extracted with methylene chloride (3×30 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by preparative TLC [2.5% NH3 (2.0 M in methanol) in CHCl3] to give the desired product (74.1 mg, 77%) as a thick oil: 1H NMR (400 MHz, CDCl3) δ 7.83 (apparent dd, 2H, J=2.9 Hz), 7.69 (apparent dd, 2H, J=2.9 Hz), 7.56 (apparent dt, 3H, J=2.9, 7.3 Hz), 7.33 (m, 4H), 7.21 (t, 1H, J=7.8 Hz), 7.09 (s, 1H), 6.81 (apparent d, 1H, J=7.8 Hz), 5.49 (apparent dd, 1H, J=5.5, 9.5 Hz), 2.98 (d, 1H, J=9.5 Hz), 2.87 (m, 2H), 2.50 (septet, 1H, J=6.7 Hz), 2.40–2.35 (m, 4H), 1.94 (m, 2H), 1.70–1.50 (m, 4H), 1.25 (d, 6H, J=7.9 Hz); ESMS m/e: 510.4 (M+H)+.

Provenance & Evidence