4-Chloro-7-Methoxyquinoline-6-CarboxaMide CAS 417721-36-9

Step 1, the synthesis of 4-cyano-3-methoxyaniline: take 134g of 4-cyano-3-hydroxyaniline, dissolve it in 500mL of N,N-dimethylformamide (DMF) and mix it well, then take 300g of the mixture , 32g of tetrabutylammonium bromide and 268g of potassium carbonate were added, the temperature of the reaction system was raised to 110°C, and 100g of dimethyl carbonate was added dropwise. After the dropwise addition, the reaction was continued for 8h. After the reaction was completed, it was cooled to room temperature, filtered, and the filtrate was reduced The solvent was distilled off under pressure, 200 g of water was added, and 500 mL of ethyl acetate was added for extraction. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was recovered from the filtrate. The volume ratio was 1:1300 to obtain 139 g of a pale yellow solid.
Step 2: Synthesis of oxime: take 74 g of the product of the first step, 4-cyano-3-methoxyaniline, dissolve in ethanol, heat to reflux, add 50 g of propionic acid dropwise, and continue to react for 5 h after the dropwise addition is completed. After the completion, the solvent was recovered under reduced pressure, and the product continued to the next step without separation.
Step 3, Synthesis of 6-cyano-7-methoxy-4-quinolinone: add 100 mL of polyphosphoric acid to the residue of the previous step, heat up to 90°C and react for 10 hours. After the reaction is completed, the reaction system is cooled After reaching room temperature, the reaction solution was poured into ice water under an ice bath, stirred vigorously for 2 h, a large amount of white solid was precipitated, filtered, and the filter cake was washed with water until neutral, and dried in vacuo to obtain 91 g of white solid.
Step 4. Synthesis of 6-cyano-7-methoxy-4-chloroquinoline: take 50 g of 6-cyano-7-methoxy-4-quinolinone, dissolve in 80 mL of thionyl chloride, heat up The reaction was refluxed for 5h. After the reaction, the unreacted thionyl chloride was recovered under reduced pressure. The residue was poured into ice water, stirred for 1h, filtered, and the filter cake was washed with water until neutral, and dried in vacuo to obtain 52g of white solid powder.
Step 5. Synthesis of 4-chloro-7-methoxyquinoline-6-amide: take 218 g of 6-cyano-7-methoxy-4-chloroquinoline, dissolve in acetic acid solution, wherein glacial acetic acid and water The volume ratio was 1:1500, heated to 80 °C for 24 hours, after the reaction, the reaction system was cooled to room temperature, 500 mL of ice water was added to the system, stirred overnight, a large amount of solid was precipitated, filtered, and the filter cake was washed with water until neutral, and dried. 222g of white solid.