反应详情

温度

60 °C

A solution of 2-Amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (1.74 g, 9.343 mmol) and triethylamine (5.2 mL, 37.31 mol) in anhydrous THF (40 mL) was heated to 60° C. and [1-(Tetrahydro-pyran-2-yl)-1H-indazol-4-yl]acetic acid (1.85 g, 7.107 mmol) in anhydrous THF (20 mL) was added followed by the addition of 1-propanephosphonic acid cyclic anhydride, 50 wt. % solution in ethyl acetate (5.2 mL, 8.735 mmol) over 1 min. The reaction mixture was heated at 60° C. for 40 min, cooled, diluted with water (150 mL) and extracted with ethyl acetate (3×150 mL). The organic layers were combined, washed with 1/1 aqueous 2N HCl/brine (100 mL), brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (33% EtOAc in hexanes) to give 4-Methyl-2-{2-[1-(tetrahydro-pyran-2-yl)-1H-indazol-4-yl]-acetylamino}-thiazole-5-carboxylic acid ethyl ester (2.23 g, 73%) as a yellow foam. MS m/e 429.5 (M+H+).

1. temperaturecooled
2. extractionextracted with ethyl acetate (3×150 mL)
3. washwashed with 1/1 aqueous 2N HCl/brine (100 mL), brine (100 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe resulting crude compound was purified by flash chromatography (33% EtOAc in hexanes)