反应详情

温度

25 °C

To a solution of 4-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acid (540 mg, 1.348 mmol) in anhydrous DMF (25 mL) was added HBTU (614 mg, 1.619 mmol), HOBt (219 mg, 1.621 mmol), H-DAP(BOC)-OME HCL (515 mg, 2.022 mmol) and triethylamine (0.9 mL, 6.457 mmol). The reaction mixture was stirred at 25° C. for 1 h and concentrated under reduced pressure to remove most of the DMF. The residue was diluted with ethyl acetate (200 mL), washed with 1/1 water/brine (40 mL), aqueous 1N HCl (40 mL), brine (40 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (40% to 100% EtOAc in hexanes) to give (S)-3-tert-Butoxycarbonylamino-2-[(4-methyl-2-{2-[1-(tetrahydropyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carbonyl)-amino]-propionic acid methyl ester (548.6 mg, 68%) as an off white foam. MS m/e 617.4 (M+H+).

1. concentrationconcentrated under reduced pressure
2. customto remove most of the DMF
3. additionThe residue was diluted with ethyl acetate (200 mL)
4. washwashed with 1/1 water/brine (40 mL), aqueous 1N HCl (40 mL), brine (40 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe resulting crude compound was purified by flash chromatography (40% to 100% EtOAc in hexanes)