1225-60-1

Theruhistin,Ayerst,US,1957

Antihistaminic.

ChEBI: Isothipendyl hydrochloride is a tertiary amino compound and an aromatic amine.

85 parts of phenylpyridyl amine, 21 parts of powdered sulfur and 1.7 parts of iodine were heated to 275°C for two hours. Evolution of hydrogen sulfide began when the mixture reached a temperature of 250°C and became vigorous when it reached 275°C. Such evolution of hydrogen sulfide diminished after about one hour at 275°C. A light oil was distilled from the reaction mixture under vacuum (pressure = 2-3 mm Hg). This oil which contained phenylpyridyl amine in addition to the thiophenylpyridyl amine was then treated at boiling temperature with approximately the theoretical amount of 2-3 normal HCl until complete solution resulted with formation of the HCl salts of the amines. The solution was then treated with 1 to 2% (based upon the substance mixture) of active carbon and then filtered hot. The nitrate was then cooled to 0°C whereupon the thiophenylpyridyl amine hydrochloride crystallized out while the phenylpyridyl amine hydrochloride remained in solution. The thiophenylpyridyl amine hydrochloride was filtered off and suspended in water and the pH adjusted with half concentrated ammonia to 8. The thiophenylpyridyl amine set free was filtered off and dried. It was in the form of gold yellow needles and had a melting point of 114°C to 115°C.
40 parts of thiophenylpyridyl amine were dissolved in 200 parts of water free toluene. After the addition of 16 parts of soda amide, the mixture was refluxed for 1% hours. Thereafter, 28 parts of dimethylaminoisopropyl chloride in 30 parts of water free toluene were dropped in and the temperature maintained at 20°C to 25°C for 30 minutes. Thereafter, the mixture was heated at 60°C for 30 minutes and subsequently refluxed for 20 minutes. Water and hydrochloride acid were then added to the reaction mixture and this mixture rendered alkaline with NaOH and then the alkalized mixture shaken out with ether. The dimethylaminoisopropyl-N9-thiophenylpyridyl amine base thus obtained was vacuum distilled. It was then converted to hydrochloride salt. The monohydrochloride salt is almost white in color and melts at 213°C to 216°C. The yield was almost 100% of the theoretical.

Antihistaminic

-20°C