Reference of 1195768-23-0 , The common heterocyclic compound, 1195768-23-0, name is N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide, molecular formula is C23H18ClF3N4O2S2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Step D: A/-{3-[5-(2-amino-4-pyhmidinyl)-2-(1 ,1 -dimethylethyl)-1 ,3-thiazol-4-yl]-2- fluorophenyl}-2,6-difluorobenzenesulfonannideIn 1 gal pressure reactor, a mixture of A/-{3-[5-(2-chloro-4-pyrinnidinyl)-2-(1 ,1 – dimethylethyl)-1 ,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (120 g) prepared in accordance with Step C, above, and ammonium hydroxide (28-30%, 2.4 L, 20 vol) was heated in the sealed pressure reactor to 98-103 C and stirred at this temperature for 2 hours. The reaction was cooled slowly to room temperature (20 C) and stirred overnight. The solids were filtered and washed with minimum amount of the mother liquor and dried under vacuum. The solids were added to a mixture of EtOAc (15 vol)/ water (2 vol) and heated to complete dissolution at 60-70 C and the aqueous layer was removed and discarded. The EtOAC layer was charged with water (1 vol) and neutralized with aq. HCI to ~pH 5.4-5.5. and added water (1 vol). The aqueous layer was removed and discarded at 60-70 C. The organic layer was washed with water (1 vol) at 60-70 C and the aqueous layer was removed and discarded. The organic layer was filtered at 60 C and concentrated to 3 volumes. EtOAc (6 vol) was charged into the mixture and heated and stirred at 72 C for 10 min , then cooled to 20C and stirred overnight. EtOAc was removed via vacuum distillation to concentrate the reaction mixture to ~3 volumes. The reaction mixture was maintained at ~65-70C for ~30mins. Product crystals having the same crystal form as those prepared in Example 58b (and preparable by the procedure of Example 58b), above, in heptanes slurry were charged. Heptane (9 vol) was slowly added at 65-70 C. The slurry was stirred at 65-70 C for 2- 3 hours and then cooled slowly to 0-5C. The product was filtered, washed withEtOAc/heptane (3/1 v/v, 4 vol) and dried at 45C under vacuum to obtain A/-{3-[5-(2- amino-4-pyrimidinyl)-2-(1 ,1 -dimethylethyl)-1 ,3-thiazol-4-yl]-2-fluorophenyl}-2,6- difluorobenzenesulfonamide (102.3 g, 88%).
The synthetic route of 1195768-23-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; GLAXOSMITHKLINE LLC; DUMBLE, Melissa; KUMAR, Rakesh; LAQUERRE, Sylvie; LEBOWITZ, Peter; WO2011/47238; (2011); A1;,
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