V. A. Chernov

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.

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).

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 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).