Diisopropylethylamine → Methyl 2-[4-((2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoylamino)butoxy]-6-hydroxybenzoate

Participants

Reaction Steps

To a solution of (2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoic acid (350 mg, 0.68 mmol) in N,N-dimethylformamide (6.54 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (318 mg, 0.719 mmol) at 0° C. under an atmosphere of nitrogen. After stirring for 15 min, methyl 2-(4-aminobutoxy)-6-hydroxybenzoate (196 mg, 0.821 mmol) and N,N-diisopropylethylamine (358 μL, 2.05 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 2 h. The reaction was diluted with ethyl acetate and quenched with sat. sodium bicarbonate solution. The aqueous phase was extracted with ethyl acetate once. The combined organic solutions were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative LCMS to afford product as a white solid (361 mg, 72% two steps). 1H NMR (500 MHz, CD3OD): δ 7.63 (d, J=15.6 Hz, 1H), 7.44 (m, 1H), 7.31 (m, 7H), 6.48 (t, J=8.0 Hz, 2H), 5.56 (m, 1H), 5.03 (d, J=13.9 Hz, 2H), 4.31 (m, 1H), 3.97 (t, J=5.6 Hz, 2H), 3.86 (s, 3H), 3.44 (m, 1H), 3.25 (m, 3H), 2.95 (m, 1H), 1.66 (m, 4H). LCMS found for C32H35BrN3O10S (M+H)+: m/z=732, 734.

Provenance & Evidence