3,5-Dichloropicolinonitrile (CAS: 85331-33-5) has been used in the preparation of Vadadustat (CAS: 1000025-07-9). Vadadustat is employed for the treatment of symptomatic anemia related to chronic kidney disease in adults undergoing chronic maintenance dialysis.
Application In Synthesis of [ 85331-33-5 ]
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With polyethylene glycol 8000; potassium fluoride; In dimethyl sulfoxide; at 160℃; for 0.5h;
[0172] 50 g (0.29 mol) of 2-cyano-3,5-dichloropyridine from Example IV, 33.6 g (0.58 mol) of potassium fluoride and 10 g of polyethylene glycol 8000 are mixed with 125 ml of DMSO and heated at 160° C. for 30 minutes. After cooling, the product is distilled out together with the DMSO under high vacuum, the distillate is added to water and, after extraction with toluene, dried over sodium sulfate. The product is reacted further as solution in toluene. [0173] Rf: 0.43 (cyclohexane/ethyl acetate=7:3)
3,5-Dichloro-pyridine-2-carbonitrile (10 g, 57 8 mmol) was dissolved in 100 mL of 95% concentrated sulfuric acid and this mixture was heated to 115 C overnight The reaction mixture was then cooled, poured over ice with strong stirring The resulting solid was filtered, washed with water and dried at 40 C under reduced pressure to give 94g (85%) of pure product as a white solid
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 50℃; for 3h;
A solution of 3,5-dichloropicolinonitrile (1.0 eq.), <strong>[39604-97-2]1-ethynyl-4-propoxybenzene</strong> (commercially available) (1.0 eq.), trans-dichlororbis(triphenylphosphine)palladium (II) (10 mol %), copper (I) iodide (20 mol %), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 50 C. for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and 10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH system (ISCO) using 0-10% ethyl acetate in hexane to give 3-chloro-5-((4-propoxyphenyl)ethynyl)picolinonitrile as a white solid.
With triethylamine;copper(l) iodide; trans-dichlorobis(triphenylphosphine)platinum(II); In N,N-dimethyl-formamide; at 50℃; for 3h;
A solution of 3,5-dichloropicolinonitrile (1.0 eq.), l-ethynyl-4-propoxybenzene(commercially available) (1.0 eq.), trans-dichlororbis(triphenylphosphine)palladium (II) (10 mol%), copper (I) iodide (20 mol%), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 500C for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH system (ISCO) using 0-10% ethyl acetate in hexane to give3-chloro-5-((4-propoxyphenyl)ethynyl)picolinonitrile as a white solid.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 50℃; for 3h;
A solution of 3,5-dichloropicolinonitrile (1.0 eq.), <strong>[769-26-6]2-ethynyl-1,3,5-trimethylbenzene</strong> (commercially available) (1.0 eq.), trans-dichlororbis(triphenylphosphine)palladium (II) (10 mol %), copper (I) iodide (20 mol %), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 50 C. for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and 10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH system (ISCO) using 0-10% ethyl acetate in hexane to give 3-chloro-5-(mesitylethynyl)picolinonitrile a as white solid.
With triethylamine;copper(l) iodide; trans-dichlorobis(triphenylphosphine)platinum(II); In N,N-dimethyl-formamide; at 50℃; for 3h;
A solution of 3,5-dichloropicolinonitrile (1.0 eq.), 2-ethynyl-l,3,5-trimethylbenzene(commercially available) (1.0 eq.), trans-dichlororbis(triphenylphosphine)palladium (II) (10 mol%), copper (I) iodide (20 mol%), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 500C for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH system (ISCO) using 0-10% ethyl acetate in hexane to give3-chloro-5-(mesitylethynyl)picolinonitrile a as white solid.
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