[F:1][CH:2]([F:13])[C:3]1[C:7]([C:8](Cl)=[O:9])=[C:6]([F:11])[N:5]([CH3:12])[N:4]=1.[CH3:14][C:15]1[CH:16]=[C:17]([CH:24]=[CH:25][CH:26]=1)[CH2:18][CH:19]1[CH2:23][CH2:22][CH2:21][NH:20]1.C(N(CC)CC)C>O1CCCC1>[F:1][CH:2]([F:13])[C:3]1[C:7]([C:8]([N:20]2[CH2:21][CH2:22][CH2:23][CH:19]2[CH2:18][C:17]2[CH:24]=[CH:25][CH:26]=[C:15]([CH3:14])[CH:16]=2)=[O:9])=[C:6]([F:11])[N:5]([CH3:12])[N:4]=1At ambient temperature, a solution of 267 mg (1.25 mmol) of 3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carbonyl chloride in 1 ml of tetrahydrofurane is added dropwise to a solution of 200 mg (1.14 mmol) of 2-(3-methylbenzyl)pyrrolidine and 127 mg (1.25 mmol) of triethylamine in 5 ml of tetra-hydrofurane. The reaction mixture is stirred for 1 hour at 70° C. The solvent is removed under vacuum and 100 ml of water are then added to the residue. The watery layer is extracted twice with ethyl acetate (2×150 ml) and the combined organic layers are successively washed by a 1 N solution of HCl, a saturated solution of potassium carbonate and filtered over a Chemelut™ cardridge to yield after concentration 350 mg of a beige oil. Column chromatography on silica gel (gradient heptane/ethyl acetate) yields 300 mg (71% yield) of [3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazol-4-yl][2-(3-methylbenzyl)pyrrolidin-1-yl]-methanone as a colourless oil (M+H=352).
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