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Thieno[2,3‐d]pyrimidines. I. A new method for the preparation of esters and amides of thieno[2,3‐ d ] pyrimidine‐6‐carboxylic acids
Author(s) -
Santilli Arthur A.,
Kim Dong Han,
Wanser Stephen V.
Publication year - 1971
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.5570080315
Subject(s) - chemistry , pyrimidine , sodium ethoxide , chloroacetyl chloride , acetic anhydride , ethanol , carboxylic acid , organic chemistry , acetic acid , sodium carbonate , medicinal chemistry , sodium , chloride , stereochemistry , catalysis
A novel method for the preparation of esters and amides of thieno[2,3‐ d ]pyrimidine‐6‐carb‐oxylic acids was described. A typical example was the direct formation of ethyl 5‐amino‐2‐methylthiothieno[2,3‐ d ]pyrimidine‐6‐earboxylate(IIIa) from 4‐chloro‐2‐methylthio‐5‐pyrimidine‐carbonitrile (Ia) and ethyl mercaptoacetate in refluxing ethanol containing sodium carbonate. Displacement of the methylthio group in IIIa by various amines gave the corresponding amino derivatives. The reactions of IIIa and related compounds with acetylating agents such as acetic anhydride or chloroacetyl chloride gave various products. Treatment of 5‐carbethoxy‐4‐chloro‐2‐phenylpyrimidine(IV) with methyl mercaptoacetate afforded the dechloro intermediate diester Va, which cyclized on reaction with sodium ethoxide to form methyl 5‐hydroxy‐2‐phenylthieno‐[2,3‐ d ]pyrimidine‐6‐carboxylate (Vla). The synthesis was expanded to include the preparation of various new 2,4,5‐trisubstituted thieno[2,3‐ d ]pyrimidine‐6‐carboxylic acid esters and amides (Charts I‐V).