Preparation method of 3-methylaminopyridine_Industrial additives

Background and overview of the preparation method of high-purity calcium carbonate 3-methylaminopyridine

3-Methylaminopyridine is an organic intermediate. 4-methyl-N-(pyridin-3-yl)benzenesulfonamide can be prepared from 3-aminopyridine as raw material, and then methylated to prepare N. 4-Dimethyl-N-(pyridin-3-yl)benzenesulfonamide, followed by deprotection affords 3-methylaminopyridine.

Preparation method of 3-methylaminopyridine

Report on the preparation method of 3-methylaminopyridine 1.

Preparation of (1) 4-methyl-N-(pyridin-3-yl)benzenesulfonamide

3-Aminopyridine (14.1g, 0.15mol) and p-toluenesulfonic acid chloride (30g, 0.157mol) were dissolved in 20mL pyridine, reacted at 100°C for 2 hours, cooled, and the reaction solution was poured into ice water to precipitate. The solid was filtered with suction and recrystallized from anhydrous ethanol to obtain 36 g of white solid with a yield of 96.7%.

Preparation of (2)N,4-dimethyl-N-(pyridin-3-yl)benzenesulfonamide

4-Methyl-N-(pyridin-3-yl)benzenesulfonamide (4.96g, 20mmol) and potassium carbonate (5.52g, 40mmol) were heated to reflux in 40mL acetone, and methyl iodide (5.67g, 40 mol) was added dropwise to the reaction solution within half an hour, and the reflux reaction was continued for 2 hours, cooled, filtered, washed the solid with acetone, and concentrated the filtrate to obtain 4.7 g of brown oil, with a yield of 89.5%.

Preparation of (3)3-methylaminopyridine

Dissolve N,4-dimethyl-N-(pyridin-3-yl)benzenesulfonamide (4.96g, 18.9mmol) in 80% concentrated sulfuric acid (20mL), and react at 100°C for 4 hours , cool, adjust the pH value of the reaction solution to 9 with ammonia water, extract with ethyl acetate, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain 1.86g of brown oil, with a yield of 91.0%.

Preparation method report 2 of 3-methylaminopyridine,

3-Aminopyridine (g, 4.25 mol sodium percarbonate) was added to triethyl orthoformate (850 g, 5.74 mol), and the temperature was slowly raised to reflux for 3 hours. The reaction solution was cooled to room temperature, and the solvent was evaporated under reduced pressure. The remaining The substance was dissolved in 1L absolute ethanol, potassium borohydride (230g, 4.26mol) was slowly added under an ice bath, and then slowly heated to 70-75°C for 10 hours. The reaction solution was cooled to room temperature, and the ethanol was evaporated under reduced pressure. The remaining yellow solid was Add 1L distilled water, stir to completely dissolve the solid, extract with toluene (500mL The yellow oily liquid is 3-methylaminopyridine, and the GC purity is 94.6%.

References

[1][China invention, China invention authorization] CN201380041007.1PI3Kδ inhibitor

[2][China invention, China invention authorization] CN201210551317.5 Preparation method of balofloxacin intermediate