反应详情

温度

0 °C

Triphenylphosphine (1.61 g, 6.15 mmol) was dissolved in methylene chloride (60 mL) and cooled to 0° C. To this solution was added N-bromosuccinimide (1.24 g, 6.97 mmol) and was stirred at 0° C. until it was completely dissolved and became light purple in color. The 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 1.36 g, 4.1 mmol) was then added and it was stirred at 0° C. for 15 min and then warmed to 25° C. and stirred for another 30 min. The mixture was cooled to 0° C. and 3-amino-pyrazole-1-carboxylic acid tert-butyl ester (0.75 g, 4.1 mmol) was added followed by N-methyl-morpholine (540 μL, 4.92 mmol). The mixture was continued to stir at 0-4° C. for 4 h. The reaction was diluted with ethyl acetate (150 mL), washed with water (50 mL), aqueous 0.1 M hydrochloric acid (2×50 mL) and saturated aqueous brine solution (2×50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 25% ethyl acetate/hexanes) afforded 3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazole-1-carboxylic acid tert-butyl ester (2.02 g, 99%) as a light yellow oil: ESI-LRMS m/e calcd for C23H30ClN3O5S [M+] 495.2, found 496.4 [M+H+], 395.5 [M−CO2tBu+H+].

1. dissolutionwas completely dissolved
2. stirringit was stirred at 0° C. for 15 min
3. temperaturewarmed to 25° C.
4. stirringstirred for another 30 min
5. temperatureThe mixture was cooled to 0° C.
6. stirringto stir at 0-4° C. for 4 h
7. washwashed with water (50 mL), aqueous 0.1 M hydrochloric acid (2×50 mL) and saturated aqueous brine solution (2×50 mL)
8. dry with materialThe organic layer was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo