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 28691-49-8,6-Chlorobenzo[d]isoxazole-3-carboxylic acid, as follows.28691-49-8
Example 54 (6-Chlorobenzo[d]isoxazol-3-yl)(2-methyl-3-phenyl-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)methanone To a solution of 6-chlorobenzo[d]isoxazole-3-carboxylic acid (52 mg, 0.263 mmol) in dichloromethane (600 muL) was added N,N-dimethylformamide (10 muL, 0.13 mmol, 0.948 g/mL) and oxalyl chloride (25 muL, 0.287 mmol, 1.45 g/mL) at 0 C. The reaction mixture was stirred at 0 C. for 5 min. To the reaction mixture was added 2-methyl-3-phenyl-4,5,6,7-tetrahydropyrazolo[3,4-c]pyridine, Intermediate 1 (55 mg, 0.258 mmol) at 0 C. The reaction mixture was allowed to warm to room temperature and stirred for 18 h. The reaction mixture was diluted with water (2 mL) and extracted with ethyl acetate (2*5 mL). The combined organic layers were washed with 10% potassium bisulfate (1*5 mL), 1 M sodium carbonate (1*5 mL) and brine (1*5 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified by reverse phase HPLC to afford the title compound (14 mg, 0.036 mmol, 13%) as an off-white powder. MS (ESI): mass calcd. for C21H17ClN4O2, 392.1; m/z found, 393.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) delta 8.15-8.12 (m, 1H), 7.96 (d, J=8.5 Hz, 1H), 7.58-7.42 (m, 6H), 4.86 (s, 2H), 3.88-3.83 (m, 2H), 3.79 (s, 3H), 2.67-2.60 (m, 2H)., 28691-49-8
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 6-Chlorobenzo[d]isoxazole-3-carboxylic acid, and friends who are interested can also refer to it.
Reference£º
Patent; Janssen Pharmaceutica NV; Ameriks, Michael K.; Chen, Gang; Huang, Chaofeng; Laforteza, Brian Ngo; Ravula, Suchitra; Southgate, Emma Helen; Zhang, Wei; US2020/102303; (2020); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics