Acetic Acid → N-Methylated pomalidomide

Participants

Reaction Steps

To a solution of NaOtBu (0.074 g, 0.769 mmol) in DMSO (0.8 mL) was added a solution of pomalidomide (0.100 g, 0.366 mmol) in DMSO (0.5 mL plus 0.5 mL rinse) dropwise. The reaction was stirred for 10 min at room temperature followed by the addition of methyl iodide (0.025 mL, 0.403 mmol). After 18 h, glacial acetic acid (0.1 mL) was added to the reaction volatiles were removed in vacuo, and the crude dark-brown residue was purified by preparative reverse phase HPLC to afford 29 (0.02 g, 19%) as light yellow powder. 1H NMR (400 MHz, DMSO) δ 7.46 (dd, J=8.4, 7.0 Hz, 1H), 7.00 (dd, J=7.6, 5.6 Hz, 2H), 6.53 (br s, 2H), 5.11 (dd, J=13.2, 5.7 Hz, 1H), 2.97-2.83 (m, 1H), 2.76 (s, 1H), 2.57-2.51 (m, 1H), 2.06-1.91 (m, 1H). MS (ESI) m/z calcd for C14H14N3O4[M+H]+ 288.3, found: 288.5.

Provenance & Evidence