Methanesulfonic anhydride → ethyl 4-((5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)(4-chloro-2-fluorophenyl)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate

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Reaction Steps

A solution of 485 mg (0.944 mmol) ethyl 4-((4-chloro-2-fluorophenyl)(hydroxy)methyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate (product from step 184.3), 0.658 ml (4.72 mmol) TEA in 19 ml CH2Cl2 was cooled down to 0° C. 411 mg (1.41 mmol) methanesulfonic anhydride was added and the solution was allowed to warm to RT. 229 mg (1.416 mmol) 5-amino-3-chloro-1-methylpyridin-2(1H)-one (intermediate W1) was added and the solution was stirred for 1.5 hour. The mixture was diluted with CH2Cl2 and washed with 1M NaHCO3 solution. The water phase was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered and evaporated. The crude product was purified by column chromatography (Silicagel, heptane, EtOAc) to give 474 mg (0.758 mmol, 80% yield) of the title compound as a brown oil. LCMS: (M+H)=619/621; tR=1.13 min (LC-MS 4). HPLC: tR=5.52 min (HPLC 7). TLC: Rf=0.09 (Heptane/EtOAc 1:2).

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