Cl.[CH2:2]([O:4][C:5]([N:7]1[C:11]([NH:12][C:13](=[O:32])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[C:10]2[CH2:33][NH:34][C:35]([CH3:37])([CH3:36])[C:9]2=[N:8]1)=[O:6])[CH3:3].C(N(CC)C(C)C)(C)C.[F:47][C:48]1[CH:49]=[C:50]([S:55](Cl)(=[O:57])=[O:56])[CH:51]=[C:52]([F:54])[CH:53]=1>ClCCl>[CH2:2]([O:4][C:5]([N:7]1[C:11]([NH:12][C:13](=[O:32])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[C:10]2[CH2:33][N:34]([S:55]([C:50]3[CH:49]=[C:48]([F:47])[CH:53]=[C:52]([F:54])[CH:51]=3)(=[O:57])=[O:56])[C:35]([CH3:36])([CH3:37])[C:9]2=[N:8]1)=[O:6])[CH3:3]To a suspension of 3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoylamino]-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester hydrochloride (1.24 g, 2.4 mmol) in dry dichloromethane (30 mL) was added N,N-diisopropylethylamine (1.67 mL, 9.6 mmol) and 3,5-difluorobenzenesulfonyl chloride (0.77 g, 3.6 mmol). After stirring at room temperature for 3 hours the mixture was diluted with dichloromethane (50 mL), washed with 1N HCl, water, saturated solution of NaHCO3, brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel eluting with ethyl acetate and then with dichloromethane/methanol 98:2 affording the title compound as white solid (1.4 g).
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