CS(C)=O.S(=O)(=O)=O.N1C=CC=CC=1.[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]([CH3:45])[C@H:26]([CH2:42][CH2:43][OH:44])[CH2:27][N:28]2[C:32]3=[N:33][CH:34]=[CH:35][CH:36]=[C:31]3[C:30]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.CCN(C(C)C)C(C)C>ClCCl>[F:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]([CH3:45])[C@H:26]([CH2:42][CH:43]=[O:44])[CH2:27][N:28]2[C:32]3=[N:33][CH:34]=[CH:35][CH:36]=[C:31]3[C:30]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1To DMSO (1 L, 1.41E+04 mmol) at room temperature was added pyridine sulfur trioxide (202.08 g, 1270 mmol) and the reaction mixture was stirred for 30 min at room temperature (solution A). In another flask, to a stirred solution of methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-hydroxybutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate (273 g, 589 mmol) and Hunig's base (0.425 L, 2433 mmol) in dichloromethane (4 L) at −10° C. was added solution A dropwise over 30 min. The reaction was stirred at −10° C. for 1 h. then quenched by adding ½ saturated brine (4 L); the aqueous layer was neutralized with solid sodium bicarbonate. The layers were then separated and the organic layer was washed with ½ saturated brine (4 L), dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography with ethyl acetate to provide the title compound.
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