[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[NH:10][CH:11]=[C:12]([I:13])[C:5]=12.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.C1COCC1>[Cl:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[N:10]([S:20]([C:17]3[CH:18]=[CH:19][C:14]([CH3:24])=[CH:15][CH:16]=3)(=[O:22])=[O:21])[CH:11]=[C:12]([I:13])[C:5]=12Under protective gas atmosphere (argon), 63.5 g (1.59 mol) of sodium hydride were suspended in 1000 ml of abs. THF. To this were added dropwise with cooling at a temperature of 0-5° C. a solution of 402 g (1.44 mol) of 4-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine in 3000 ml of abs. THF, and the reaction mixture was left to stir for a further 15 minutes after completion of addition. Subsequently, 358 g (1.88 mol) of p-toluenesulphonyl chloride were added in portions to the reaction mixture in such a way that the temperature was kept between 5-10° C. After the addition had ended, the mixture was allowed to come to 20° C. and stirred at this temperature for a further hour. On completion of conversion (TLC monitoring of conversion), the reaction mixture was admixed with 20 l of saturated NaHCO3 solution and 10 l of ethyl acetate, and extracted, and the organic phase was removed. The aqueous phase was extracted twice more with 10 l each time of ethyl acetate, and the organic phases were combined, dried and freed of volatile constituents in a water-jet vacuum. To purify the crystalline crude product, it was taken up in dichloromethane and chromatographed using silica gel (CH2Cl2: 40/60 petroleum ether=3:7). After the solvents had been removed, the crystal slurry was extractively stirred in diethyl ether, and the solids were filtered off with suction and dried at 20° C. under high vacuum. A total of 372 g (0.86 mol, 60%) of 4-chloro-1-(toluene-4-sulphonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine were isolated as a colourless solid.
불러오는 중…
