Vol. 70 from 250 cc. of hot ethanol. The yield of pure product was 1 g., m. p. 185-188°dec.Anal. Calcd. for C22H39O6NS: N, 3.14. Found: N (Dumas), 2.84, basic N (perchloric acid titration in acetic acid), 2.76.The product was soluble in sodium bicarbonate solutions and in hot dilute hydrochloric acid solution. Alkaline titration indicated the presence of one carboxyl and one lactone group. The reaction product obtained from cysteine and Afl.r-angelicalactone11 when titrated with perchloric acid showed the absence of a basic amino group; protolichesterinic acid appears to have added cysteine through the -SH group without secondary involvement of the amino group. Antibacterial Tests.-Tests against the Streptococcus, Staphylococcus and Bacillus typhi were conducted in tryptose phosphate medium. The inoculum was a 1:1000 dilution of a twenty-four-hour culture of the organism and incubation was for eighteen hours at 37°. The anaerobe was tested in Bacto-Anaerobe Medium with Dextrose. The acid-fast organisms, B. tuberculosis ranae and the human tuberculosis strain H37Rv were grown in submerged culture in Youmans' modification14 of Proskauer-Beck synthetic medium. The inoculum with ranae was a (14) Composition: Asparagin, 0.5%; primary potassium acid phosphate, 0.5%, potassium sulfate, 0.05%; magnesium citrate, 0.15%; and glycerol, 2% in distilled water.1:100 dilution of a forty-eight hour culture in Long's synthetic medium; incubation was for forty-eight hours at 37°. An inoculum of 0.02 mg. of fresh bacteria per cc. of test medium was used with H37Rv; incubation at 37°w as for fourteen days, excellent growth being evidenced after eight days.Acknowledgment.-We are indebted to M. E. Auerbach and Staff for analytical data, to Dr. F. C. Nachod for surface-tension measurements, and John W. Klimek for antifungal tests.
Relatively few di-(ary1amino)-pyrimidines and amino-arylaminopyrimidines are recorded in the literature.1.2~a~4~6 These compounds were prepared by reawing a halo-or ethylmercapto-pyrimidine in the liquid amine and were limited to those containing simple.ary1 groups such as phenyl and tolyl. In the precedipg paper of this series,6 the condensation of 2-amino-4-chloropyrimidine and aniline was studied to detennine the rate of reaction under varying conditions of alkalinity and acidity. The compound formed, 2-amino-Panilinopyrimidine, was isolated and studied pharmacologically. It caused a 'presser response in anesthetized dogs equal to that of benzedrine but of shorter duration. It also appeared to have analgetic activity.' Since the structure of this compound differs ' widely from other compounds having similar pharmacological activity, a number of compounds having substituents in the benzene ring were prepared.All of the arylamines and halo-aminopyrimidines used are commercially available or adequately described in the literature. The condensation of amine and heterocycle was carried out under the optimum reaction conditions previously described.6 The yields were nearly theoretical. Morpholine was also condensed with 2amino-4-chloropyrimidine, using the same procedure, in yields of 66-75%. The compounds so formed are now being studied for pharmacological activity.Experimental 2-Amino4anilinopyrimidinrimidine-tenth mde of aniline, 0.1 mole of 2-amino-4-chloropyrimidine and 1 ml. of hydrochloric acid in 100 ml. of water were refluxed for thirty minutes. A clear solution was formed, which was charcoaled (Darco) and filtered while hot. A test for unreacted amine indicated that over 99% reaction had occurred. The filtrate was cooled, made strongly alkaline with 10 N sodium hydroxide and the precipitated product filtered off and recrystallized from alcohol-water. The over-all yield was 92%. The monoacetate salt was formed by dissolving the base in hot dilute acetic acid and cooling. The diacetate was prepared by solution of the base in glacial acetic acid and precipitating with anhydrous ether. These compounds were dried in ULUW (1 mm.) for twentyfoy: hours at room temperature. The diacetate loses one mole of acetic acid when heated in wcuo. The hydrochloride was formed by solution of the base in alcoholic Pharmacological work under the supervision of Drs. C. C. PfeifIer and E R. Loew of our laboratories.hydrochloric acid, addition of five volumes of butyl acetate and crystallization started by scratching. The crys; tals were filtered off and dried twenty-four hours at 100 WGW. Similar procedures were followed in preparing compounds 3, 15, 16, 17, 18 and '19 of the table. The remainder were prepared by carrying out the condensation in the same manner but after charcoaling and filtering, an equal volume of concentrated hydrochloric acid was added and the solution chilled in an ice-bath. The produit.was filtered off and recrystallized from dilute hydrochloric acid. To obtain the free bases of these hy ochlorides, aqueous...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.