反应详情

(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid (0.026 g, 0.000049 mol;) was dissolved in N,N-Dimethylformamide (2 mL, 0.03 mol;) and 2.0 M of Methylamine in Tetrahydrofuran (0.2432 mL) and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (0.024 g, 0.000063 mol;) were added. The reaction was checked after 2 hours and it showed that both product and starting material were present. The reaction was pushed by further addition of methylamine and HATU, but the reaction could not be pushed past 60-70 percent completion. The reaction was therefore worked up by concentration then dissolving in methylene chloride and washing 1× with saturated bicarbonate, and 1× with brine before drying with magnesium sulfate and concentration. The crude showed very little starting material left after workup, the acid was most likely removed by the bicarb wash. The crude was dissolved in DMSO and injected onto the Gilson for HPLC purification to give the pure product at 1.20 548.54. ES (+) MS m/e=548.54; NMR (400 MHz, DMSO-d6) δ ppm 2.55 (s, 3H), 2.78 (d, 2H, J=7 Hz), 5.22 (m, 2H), 6.66 (t, 1H, J=8 Hz), 6.97 (d, 1H, J=3 Hz), 7.14-7.21 (m, 3H), 7.38-7.49 (m, 2H), 7.79 (m, 1H), 8.2-8.25 (m, 2H), 8.29 (m, 1H), 8.4 (dd. 1H), 10.25 (d, 1H), 11.97 (s, 1H)

1. customthe reaction could not
2. concentrationThe reaction was therefore worked up by concentration
3. dissolutionthen dissolving in methylene chloride
4. washwashing 1× with saturated bicarbonate, and 1× with brine
5. dry with materialbefore drying with magnesium sulfate and concentration
6. waitleft after workup
7. customthe acid was most likely removed by the bicarb
8. washwash
9. dissolutionThe crude was dissolved in DMSO
10. custominjected onto the Gilson for HPLC purification
11. customto give the pure product at 1.20 548.54