89979-12-4, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 89979-12-4 as follows.
Example 12 Preparation of Intermediate 11 [0467] [0468] HATU (1.37 g, 3.59 mmol) was added to a solution of 5-chloro-2-(methylsulfonamido)benzoic acid (823 mg, 3.29 mmol) in DMF (15.0 mL), and the reaction mixture was stirred at room temperature. After 1 h, a solution of crude intermediate 6 (220 mg, 2.99 mmol) in DMF (1 mL) was added followed by the addition of triethylamine (2.00 mL, 14.3 mmol), and the reaction mixture was stirred at room temperature for 19 h. The reaction mixture was partitioned between ethyl acetate (250 mL) and saturated aqueous sodium bicarbonate solution (200 mL), and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate solution (200 mL) and saturated sodium chloride solution (200 mL), was dried over Na2SO4, and was concentrated under reduced pressure. The crude residue was purified via SiO2 column chromatography (12 g SiO2 Combiflash HP Gold Column, 0-100% ethyl acetate/hexanes) to afford intermediate 11 (736.2 mg, 51% (2-steps)) as a white solid. [0469] 1H NMR (CDCl3, 400 MHz): delta 10.05 (br s, 0.2H), 9.13 (br s, 1H), 8.95 (br s, 1H), 8.81 (br s, 0.2H), 7.70 (d, J=8.8 Hz, 1H), 7.56 (d, J=8.8 Hz, 0.2H), 7.40 (dd, J=8.8, 2.4 Hz, 1H), 7.33 (d, J=2.4 Hz, 1H), 7.31 (d, J=4.4 Hz, 0.2H), 6.45 (s, 1H), 6.40 (br s, 0.2H), 6.28 (br d, J=4.4 Hz, 1H), 5.01 (br s, 0.2H), 4.54 (br d, J=14.0 Hz, 0.2H), 3.35 (br d, J=13.2 Hz, 1H), 3.15-3.03 (m, 1H), 2.92 (s, 3H), 2.39 (s, 3H), 2.13-1.98 (m, 1H), 1.90-1.59 (m, 2H), 1.59-1.31 (m, 3H). [0470] 13C NMR (CDCl3, 100 MHz): delta 167.09, 156.12, 153.13, 147.86, 135.68, 131.79, 131.66, 131.38, 130.12, 125.91, 125.44, 117.08, 93.74, 47.65, 44.07, 39.81, 27.83, 25.47, 19.78, 16.90. [0471] LCMS (ESI) m/z 482.1 [M+H]+, tR=2.79 min. [0472] HPLC tR (min), purity %: 5.438, 99% [0473] Rf=0.47 (50% EtOAc/hexanes). [0474] Chiral HPLC, 99% ee (Chiralpak IC 5 mM, 4.6¡Á150 mm, 10-95% MeCN/H2O, 0.05% trifluoroacetic acid modifier) (S)-isomer tR=29.739 min, (R)-isomer tR=29.495 min.
According to the analysis of related databases, 5-Chloro-2-(methylsulfonamido)benzoic acid, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Siegel, Dustin; Sperandio, David; Yang, Hai; Sangi, Michael; Parrish, Jay P.; Hui, Hon Chung; US2013/273037; (2013); A1;,
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