952
COMMUNICATIONS TO THE
VOl. 80:
EDITOR
soil near Fuji City, Shizuoka P r e f e ~ t u r e ,is~ reported 259 (9480), 280 (10,950)1, followed by decarboxylation of its copper salt in quinoline1aa t 210' to give the to be active against Mycobacterium tuberculosis H37Rv known 4-aminopyrrolo [2,3-d]pyrimidine ( I b ) , 4 the and Candida albicans.a I t has been shown to have aglycone of Tubercidin. This degradation of I I b thus structure I I a on the basis of spectral evidence and degr a d a t i ~ n . ~ . ~Tubercidin O has not been synthesized,j.ll constitutes an independent synthesis of Ib. even though its aglycone I b is a known c o m p o ~ n d . ~ We wish to report a t this time another b u t related The aglycone I I b of Toyocamycin is not known; i t pyrrolo [2,3-dJpyritiiidine synthesis cia pyrrole intermediates. The condensation of aminoacetone and of was not prepared from the antibiotic and has not been w-aminoacetophenone (as representative examples of synthesized, presumably because the only previously a-aminoketones) with malononitrile to give 5-amino-4available synthetic route to pyrrolo [2,3-d]pyrimidines, cyano-3-methyl- and 3-phenylpyrrole has recently t h a t discussed by Davol17 via pyrimidine intermediates, is not applicable to the preparation of 4-amino-5been reported by G e ~ a 1 d . I ~We have found t h a t cyanopyrrolo [2,3-dlpyrimidine (Ilb). these o-aminonitriles can be converted to 4-amino-5\Ve wish to describe in this communication a simple methylp yrrolo [ 2,3-d ]pyrimidine ( I X , m.p. 257-258 ', 5070 yield) and 4-amino-5-phenylpyrrolo [2,3-d]pyrimisynthesis of the pyrrolo [2,3-d]pyrimidine ring system dine (X, m.p. 259-261', 35% yield), respectively, by utilizing pyrrole intermediates which has permitted the preparation of the aglycones I b and I I b of both initial reaction with ethyl orthoformate to give the 5ethoxymethyleneamino derivatives, followed by treatantibiotics. l 2 ment with alcoholic ammonia to give the 4-cyano-5Tetracyanoethylene was converted by the action of hydrogen sulfide to 2,5-diamino-3,4-dicyanothiophene formamidino derivatives and final cyclization with sodium niethoxide in methanol. Several 4-substituted (111), which was rearranged with alkali to %aminoamino derivatives of 5-methyl- and 5-phenylpyrrolo3,4-dicyano-2-mercaptopyrrole(IV) as described by [2,3-d]pyrimidine were prepared directly by reaction ~ of I V with methyl Middleton, et ~ 1 . l Treatment of the above 5-ethoxymethyleneamino intermediates orthoformate followed by alcoholic ammonia gave 4with primary amineszo (XI, m.p. 250-251.5', 35% an1ino-5-cyano-6-rnethylmercaptopyrrolo [ 2,3-d ] pyrimidineI4 [V, m.p. 317-318' dec., 57% yield, X2zoH yield; XJI, m.p. 124-127', 19% yield; X I I I , n1.p. 286.5-288', 38y0 y!eld). I t would appear that ap231 mp ( e 16,900) and 301 (17,600); infrared, CK propriate combinations of the above two synthetic band a t 2225 cm.-l]. Desulfurization of V with routes should make readily available a wide variety of Raney nickellj in aqueous ammonium hydroxide then 4-aminopyrrolo [2,3-d]pyrimidines structurally related gave 4-amino-5-cyanopyrrolo [2,3-d]pyrimidine [IIb, to Tubercidin and Toyocamycin. m.p. > 360', 35% yield; 226 m,u ( e 10,700), 277 (13,700), 287 (975U)I6; infrared, CN band a t NHR' 2225 cm. - I ] , the aglycone of Toyocamycin. Alternatively, refluxing IV with formamidine acetate17 in 2-ethoxyethanol gave 4-amino-5-cyano-Gmercaptopyrrolo [2,3-d]pyrimidine (VI), which was characterized as its 6,7-dimethyl derivative (VII, m.p. IX, R = CH3; R' = H 315-317' dec.) by treatment with methyl iodide and CsHs; R ' = H X, R XI, R = R ' = CHI alkali. Analogous methylation of V also gave VII. XII, R = CHI; R ' = (CH?);
