Premium
Analogs of tetrahydrofolic acid. XXXIX . selective bromoacylation of polyfunctional molecules for synthesis of active‐site‐directed irreversible enzyme inhibitors
Author(s) -
Baker B. R.,
Santi Daniel V.,
Coward James K.,
Shapiro Howard S.,
Jordaan Johannes H.
Publication year - 1966
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.5570030407
Subject(s) - chemistry , amine gas treating , acylation , derivatization , protonation , organic chemistry , stoichiometry , molecule , acid anhydride , base (topology) , combinatorial chemistry , polymerization , aqueous solution , polymer , catalysis , high performance liquid chromatography , ion , mathematical analysis , mathematics , epoxy
A number of methods for selective bromoacylation of side‐chain amino groups on 2‐amino‐4‐pyrimidinols or 2,4,6‐triaminopyrimidines have been developed for these extremely sensitive products. The choice of method depends upon whether (a) the aminopyrimidine is a stronger base than the amine to be bromoacylated, (b) as weak a base as the amine to be bromoacylated but the amine is more reactive, (c) the amine group to be bromoacylated is a strong aliphatic amine. In case (a) the aminopyrimidine can be protonated to protect it from acylation with an anhydride; in case (b), the reaction with an anhydride is controlled by temperature, stoichiometry, and time of reaction; in case (c), the reaction is selectively controlled by use of the less reactive p ‐nitrophenyl esters. Other difficulties were solved such as (a) proper characterization of the products when combustion analyses were unsatisfactory due to polymerization; in these cases a combination of thin layer chromatography, color reactions, and derivatization were employed; and (b) insolubility leading to overreaction on the aminopyrimidine which was solved with partial aqueous systems.