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Development of a new synthesis of 3‐(1 H ‐tetrazol‐5‐yl)‐4(3 H )‐quinazolinone, sodium salt via an amidine intermediate
Author(s) -
Vinogradoff Anna P.,
Peet Norton P.
Publication year - 1989
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.5570260118
Subject(s) - chemistry , amidine , anthranilic acid , quinazolinone , triethyl orthoformate , sodium salt , base (topology) , salt (chemistry) , medicinal chemistry , combinatorial chemistry , stereochemistry , organic chemistry , inorganic chemistry , catalysis , mathematical analysis , mathematics
A new synthesis of the recently reported 3‐(1 H ‐tetrazol‐5‐yl)‐4(3 H )‐quinazolinone, sodium salt ( 1 , MDL‐427), an experimental mediator release inhibitor, was developed from: (1) reaction of 5‐aminotetrazole 3 and triethyl orthoformate 6 to give ethyl N ‐(1 H ‐tetrazol‐5‐yl)formimidate 8 , (2) reaction of methyl anthranilate and imidate 8 to give amidine 11 , and (3) treatment of 11 with base to give 1 . Investigation of each of these steps independently led to a significantly more efficient, facile and higher‐yielding 1‐pot process. A brief examination of anthranilic acid 13 and its salts and derivatives 14 to 17 in this process found them to have dissimilar reactivities. The formation of amidine 11 as an isolable intermediate was unusual, as was its failure to cyclize under standard neutral or acidic conditions. The absolute requirement for base to effect cyclization of 11 appears to be unprecedented.