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Synthesis of thiopyrano[2,3‐ d ] pyrimidines and thieno[2,3‐ d ]pyrimidines
Author(s) -
Santilli Arthur A.,
Scotese Anthony C.
Publication year - 1977
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570140301
Subject(s) - chemistry , pyrimidine , acetic anhydride , sodium hydroxide , hydrochloride , benzaldehyde , acetic acid , hydrolysis , ethanol , sodium acetate , medicinal chemistry , ethyl acetate , derivative (finance) , alkaline hydrolysis , organic chemistry , stereochemistry , catalysis , financial economics , economics
The reaction of 4‐chloro‐5‐cyano‐2‐methylthiopyrimidine (I) with ethyl mercaptosuccinate (II) in refluxing ethanol containing sodium carbonate has afforded diethyl 3‐amino‐2‐(methyl‐thio)‐7 H ‐thiopyrano[2,3‐ d ]pyrimidine‐6,7‐dicarboxylate (IV). Displacement of the methylthio group in IV with hydrazine gave the corresponding hydrazino derivative which underwent Schiff base formation with benzaldehyde or 2,6‐dichlorobenzaldehyde. Treatment of IV in refluxing acetic anhydride afforded the corresponding diacetylated amino derivative. Partial saponification of IV with sodium hydroxide gave 5‐amino‐2‐(methylthio)‐7 H ‐thiopyrano‐[2,3‐ d ]pyrimidine 6,7‐dicarboxylic acid 6 ethyl ester (VIII). The reaction of 4‐amino‐6‐chloro‐5‐cyano‐2‐phenylpyrirnidine (XI) with II resulted in the formation of ethyl 4‐amino‐6‐(ethoxy‐carbonyl)‐5,6‐dihydro‐5‐amino‐2‐phenylthieno[2,3‐ d ]pyrimidine‐6‐acetate (XIII) which when subjected to hydrolysis gave ethyl 4,5‐diamino‐2‐phenylthieno[2,3‐ d ]pyrimidine‐6‐acetate isolated as the hydrochloride (XIV). Diazotization of IV with sodium nitrite in acetic acid unexpectedly afforded diethyl 5‐(acetyloxy)‐6,7‐dihydro‐6‐hydroxy‐2‐(methylthio)‐5 H ‐thio‐pyrano[2,3‐ d ]pyrimidine‐6,7‐diearboxylate (XV). Several structural ambiguities were resolved by ir and pmr spectra.