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Novel Solid‐phase and Solution‐phase Synthetic Methods for Trisubstituted Thieno[3,2‐ d ]pyrimidine Derivatives
Author(s) -
Jeon MoonKook,
Kim JungGyu,
Lee DuckHyung
Publication year - 2016
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.10878
Subject(s) - chemistry , pyrimidine , phosphonium , amination , hexafluorophosphate , aryl , solid phase synthesis , amide , medicinal chemistry , phosphonium salt , thiophene , alkyl , organic chemistry , ionic liquid , stereochemistry , salt (chemistry) , catalysis , peptide , biochemistry
The coupling of 7‐aryl‐3,4‐dihydro‐4‐oxothieno[3,2‐ d ]pyrimidine‐2‐carboxylic acid with a primary alkylamine‐loaded acid‐sensitive methoxy benzaldehyde (AMEBA) resin, a benzotriazol‐1‐yloxytris(dimethylamino)phosphonium hexafluorophosphate ( BOP )‐mediated amination reaction, and cleavage from the solid support yielded N ‐alkyl‐4‐(alkylamino)‐7‐arylthieno[3,2‐ d ]pyrimidine‐2‐carboxamide derivatives. The progress of the reactions on solid phase was monitored through attenuated total reflectance‐ FTIR spectroscopy and was compared with representative solution‐phase surrogates. Additionally, N ‐acylation (acid chloride, InF 3 , CH 3 CN , room temperature) and cyclization ( DBN , 1,4‐dioxane, 80°C) of a 3‐amino‐4‐(4‐ t ‐butoxycarbonylphenyl)thiophene‐2‐carboxamide intermediate under previously unreported conditions provided 2‐substituted thieno[3,2‐ d ]pyrimidin‐4(3 H )‐one derivatives, which were subsequently converted to 2‐substituted 4‐alkylamino‐7‐[4‐(alkylaminocarbonyl)phenyl]thieno[3,2‐ d ]pyrimidine derivatives through a reaction sequence consisting of a BOP‐mediated amination reaction, t ‐butyl deprotection, and amide formation.