K. Yu. Novitskii

Derivatives of pyrrolo [2, 3-d] pyrimidine

Earlier we reported the preparation of the previously unknown 2-methyl-4-oxo-3,4-dihydropyrrolo[3,2-d]pyrimidine-7-aldehyde, and from it the nitrile (I) and the pyrrolo[3,2-d]pyrimidine unsubstituted at position 7 (II). Nitrile I and pyrrolopyrimidine II were used in the present work for the preparation of pyrrolo[3,2-d]pyrimidines containing, as substituents in position 4, amino groups (Va-e and Via-d) or sulfhydryl (Vf and Vie). To prepare these compounds, 4-oxopyrrolo[3,2-d]pyrimidines I and II were treated with phosphorus oxychloride, and the 4-chloro derivatives (III and IV) thus obtained, were treated with nucleophilic reagents, such as amines or sodium hydrosulfide. It was observed that the presence of the nitrile group in the 7 position increased the reactivity of the chlorine, compared to the pyrrolopyrimidine unsubstituted at the 7 position. The chloroderivative III reacts with amines in boiling ethanol to form the amino derivatives Va-c. III reacts with aniline hydrochloride or withglycine methyl ester in water to form Vd or Ve. Under analogous conditions the chlorine atom in compound IV is not replaced by an amine residue. The reaction proceeds only in boiling butanol.

Study of a pyrrole [3,2-d]pyrimidine series. II

Among these , we found compounds which dep re s sed the in v i t r o growth of lactobaci l l i . Some c o m pounds with th ioes te r groups at the 4 posi t ion exhibited a high tuberculos ta t ic p rope r ty which was to a high degree re ta ined in the p r e s ence of no rma l horse s e r u m [2]. We cons idered it of in te res t to synthesize type A pyr imid ines , but with a phenyl group (type B) instead of the methyl at posit ion 6, and to study their b iologic act ivi ty .

Arylation of furylglyoxylic acid by the meerwein reaction

We also used the Meerwein reaction to synthesize in addition to acids (la) and (Ib), the hitherto unknown glyoxylic acids (Ic)-(le). We isolated 2,5-bis(p-ethoxycarbonylphenyl)furan as a by-product from the arylation of furylglyoxylic acid with the p-(ethoxycarbonyl)benzene diazonium cation. We have already reported the formation of 2,5-bisarylfurans in the arylation of pyromucic acid [2] and acylfurans [I].

Pyrrolo[3,2-d]pyrimidines. III. 7-Aminomethyl-substituted pyrrolo[3,2-d]pyrimidines

To a solution of 0.02 mole of the benzodihydrothiochromene (VI-VIII) in 0.04 mole of triethylsilane was added 0.06 mole of dry trifluoroacetic acid. The reaction mixture was warmed to 60-80~ and after 3-5 min the starting material had been completely converted into the corresponding sulfide (XIV-XVI), which separated as colorless crystals. These were isolated, washed with alcohol, and dried to give 95-98% of the sulfide (XIV-XVI), the melting points of which corresponded with those of the sulfides obtained by reacting the diketone (I, II, or V) with H2S in trifluoroacetic acid. 2-Phenyl-4-p-methoxyphenyl-7,8-benzo-5,6-dihydro(XIX) and 2,4-diphenyl-5,6-benzo-7,8-dihydrochromylium fluoroborates were synthesized as described in [i], purification being effected by reprecipitation from chloroform with ether (Table 2).

Application of the vilsmeier reaction to the synthesis of derivatives of pyrrolo [3,2-d] pyrimidine-7-carboxaldehyde

M. V. Rubtsov and A. G. Baichikov, Synthetic Pharmaceutical Chemistry Preparations [in Russian], Moscow (1971), p. 138. Dictionary of Organic Compounds [in Russian], Vol. 2, Moscow (1949), p. 531. V. I. Khmelevskii and E. I. Abramova, Zh. Obshch. Khim., 28, 1970 (1958). Japanese Patent 2722; Chem, Abstr., 49, 2492 (1955), V. M. Nesterov, L. A. Kucherya, and V. M. Drevina~ Khim.-Farm. Zh., No. 4, 71-72 (1977).

Investigations in the pyrrolo[3,2-d] pyrimidine series

It was es tabl ished that an t ibac te r ia l act ivi ty depended not only on the group introduced into posi t ion 4, but a Iso on the c h a r a c t e r of the subst i tuent in posi t ions 2 and 6 [3]. We desc r ibe an in teres t ing p r epa ra t i on of the analogous de r iva t ives of pyr ro lo [3 ,2 -d]pyr imid ine of type C, in which a phenyl group is s i tuated in pos i t ion 2 and a methyl in posi t ion 6, and an invest igat ion of t he i r b io logica l act ivi ty . The synthesis of these 6me thy l -2 -pheny lpyr ro lo [3 ,2 -d ]pyr imid ine de r iva t ives was accompl i shed according to the following scheme:

Synthesis and tuberculostatic activity of 5-aryl-2-(2-hydroxyethyl)furans and their carbamoyl derivatives

Arylfuryllithium, formed by the interaction of arylfurans with butyl lithium, was treated in si~ with ethylene oxide to give the hydroxyethyl derivatives la-d. The structure of the compounds obtained was confirmed by the presence of absorption bands in the 3350-3500 and 1028-1055 cm -I regions of the IR, and of proton signals for the OH at 2.19 ppm (s),* and for the methylene group at 2.85 ppm (B-CH2, t) and 3.82 ppm (a-CHu, t) in the NMR spectrum.

Synthesis and germistatic activity of syn and anti isomers of arylfurfural oxime acetates

i. M. A. Iradyan, R. A. Aroyan, and A. A. Aroyan, Arm. Khim. Zh., No. i0, 851 (1973). 2. A. A. Aroyan, M. A. Iradyan, and R. A. Aroyan, Arm. Khim. Zh,, No. 2, 136 (1973). 3. US Patent No. 3775478 (1973); Chem. Abstr., 80, 36,880 (1974). 4. US Patent No. 3714179 (1973); Chem, Abstr., 78, 111,325 (1973). 5. West German Patent No. 2104158 (1971); Chem. Abstr., 75, 151,791 (1971). 6. US Patent No. 3715367 (1973); Chem. Abstr., 78, 136295 (1973). 7. Canadian Patent No. 736484 (1966); Chem. Abstr., 65, 12211 (1966). 8. R. T. Aplin, M. Fisher, and D. Becner, J. Am. Chem. Soc., 21, 4888 (1965). 9. A. A. Aroyan, T. R. Ovsepyan, R. G. Melik-Ogandzhanyan, et al., Arm. Khim. Zh., No. 5, 406 (1969). i0. A. S. Azaryan, Sh. A. Avetyan, and A. A. Aroyan, Arm. Khim. Zh., No. 2, 151 (1972). ii. P. R. Ovsepyan and A. A. Aroyan, Arm. Khim. Zh., No. i, 42 (1972). 12. A. A. Aroyan, To R. Ovsepyan, and P. R. Akopyan, Arm. Khim. Zh., No. 7, 629 (1970).

Advances in the field of developing synthetic drugs

Over the past decade, research on new drugs and their introduction into use in all countries was substantially modified. New drug preparations must have indisputable advantages over the medications of the same type of action already in use. C~vernment requirements as to the safety of new drugs increased in an extraordinary manner. The testing for chronic toxicity, teratogenicity, carcinogenicity, and other indications of the harmlessness of preparations is a very complex process and requires the coordinated effort of chemists, biologists, biochemists, and clinicians. The requirements have also significantly increased for the technological documentation necessary for organizing the manufacture of the preparation and pharmaceutical forms and in working out the methods of drug analysis. At present only large research organizations are capable of properly conducting all these investigations. Such organizations are made up of all the departments necessary for coping with the tasks mentioned above.

Synthesis and biological properties of aryloxyfuran derivatives

i. M. P. LaMontagne, J. Med. Chem., 16, 68-72 (1973). 2. E. F. Elslager and D. F. Worth, US Patent No. 2925417 (1960); Ref. Zh. Khim., No. 5L285 (1962). 3. W. C. Austin, W. Courtney, J. C. Danilewicz, et ai., Nature, 212, 1273-1274 (1966). 4. W. J. Ross, W. B. Jamieson, and M. C. McCowen, J. Med. Chem., __15, 1035-1040 (1972). 5. R. B. Burrows, and A. P. Phillips, US Patent No. 3772287 (1973); Ref. Zh. Khim., , No. 21H381P (1974). 6. V. A. Anisimov and A. F. Pozharskii, Khim. Geterotsikl. Soedin., 137-138 (1974). 7. L. Bellamy, New Data on the Infrared Spectra of Complex Molecules [Russian translation], Moscow (1971). 8. A. F. Pozharskii, I. S. Kashparov, P. Dzh. Kho!is, et al., Khim. Geterotsikl. Soedin., 543-552 (1971). 9. E. Reimann, Justus Liebigs Ann. Chem., 750, 109-114 (1971). i0. W. West (editor), Chemical Applications of Spectroscopy, New York (1956), p. 787. ii. Tukumi Katsumoto, Bull. Chem. Soc. Japan, 33, 242-250 (1960). 12. A. I. Krotov, Bases of Experimental Therapy of Helminthosis [in Russian], Moscow (1973).