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Several 9-furfuryl-6-substituted purines were synthesized by reacting 9-furfuryl-6-chloropurine (5) with the corresponding nucleophilic reagent. The mother compound (5) was prepared by direct cyclization of 4-furfurylamino-5-amino-6-chloropyrimidine (4) with a mixture of ethyl orthoformate and acetic anhydride. The diaminopyrimidine (5) was prepared by treatment of 4,6-dichloro-5-aminopyrimidine with furfurylamine in boiling water.Canadian Journal of Chemistry, 46, 419 (1968) In the synthesis of various potential antagonists of the natural purines 9-methyl-6-chloropurine (1) has shown the same order of activity against Adenocarcinoma 755 in C-57 black mice as 6-chloropurine3 (2), while two other 9-methyl-6-substituted purines have shown less activity against this tumor. 9-Ethyl-6-chloropurine (3) and 9-propyl-6-chloropurine (4), synthesized by Montgomery and Temple, have also shown the same kind of activity.Due to the structural similarity between naturally occurring metabolic purine ribonucleosides, deoxyribonucleosides, and 9-furfuryl-6-substituted purines, the investigation of the biological activity of 9-furfuryl-6-substituted purines could be of some interest. A comparison of the biological activity of 9-f~1rfuryl-6-chloropurine with that of 9-methyl-, 9-ethyl-, 9-propyl-, and 9-phenyl-6-chloropurine (5) would be especially desirable.Thirteen such derivatives of purine were synthesized through the method devised by Robins and Lin (1) and sent to the Cancer Chemotherapy National Service Center, National Institutes of Health, Bethesda, Maryland, for screening their biological activities. The mother compound 9-furfuryl-6-chloropurine (5) amino-5-amino-6-chloropyrimidine (4) with a mixture of ethyl orthoformate and acetic anhydride.Treatment of several aliphatic and aromatic amines with 5 in boiling amyl alcohol yielded corresponding amino derivatives in fairly good yield. Cyclization of 4-furfurylamino-5-amino-6-chloropyrimidine by refluxing with 97 % formic acid failed to yield 9-furfuryl-6-hydroxypurine (6). A black sticky polymeric residue was the only product that could be isolated. The ring cleavage of furfuryl ring in the boiling formic acid could cause the formation of this polymeric residue. 9-Furfuryl-6-hydroxypurine (6) was prepared easily by treatment of the mother coinpound (5) with 1 N sodium hydroxide in good yield. 9-Furfuryl-6-methoxypurine (9) was prepared by treatment of 5 with sodium inethoxide. 9-Furfuryl-6 -aminopurine (9-furfuryladenine) (8) was prepared by heating 5 with excess concentrated ammonium hydroxide at 130" in a steel Parr bomb. 9-Furfuryl-6-mercaptopurine (7) was prepared in high yield by treatment of 5 with thiourea. The ultraviolet absorption spectra of the 9-furfuryl-6-substituted purines are in general very similar to that of 9-methyl-6-substituted purines. Biological Activities9-Furfuryl-6-mercaptopurine (7) was found to be active at 112 mg/Kg (TIC, 31 %) against Adenocarcinoma 755. 4,6-Difurfurylamino-5-nitropyrimidine (1) was found to be non-toxic and inactive at 12...

JUSE 1%6NOTES 695 from et,hyl acetate-ethanol, the cryst'als had n1.p. and mixed m.p. 135-137".The foiirth component ol 0.042 g. of sirup was a mixture of D-xylose and the barium salts of methylated uronic acids. An aqueous solution of the sirup was stirred with a mixture of Amherlite IR-120 (H) and IR-4B (OH) resins, filtered, and concentrated to 0.011 g. of sirup. Its chrom:ttographic behavior in solvents (A) and (C) was identical to that shown The fift,h component consisted of 0.213 g. of amorphous barium salts of methylated uronic acids, as indicated by barium analysis and chromatography of the free acids. The small yield and mixed nature made it. undesirable to idmtify individual constituents, some of whith were possibly aldohiouronic acids.hy D-X!.lOSe.

The nuclear magnetic resonance chemical shifts and coupling constants are reported for seven aryl nitrogen derivatives of estratriens. This study confirmed the position of the group on the aromatic ring.