The 4,6-Pyrimidine dicarboxylic acid is an interme
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Posted On: 04/16/2021 2:14:13 PM
The 4,6-Pyrimidine dicarboxylic acid is an intermediate compound used in the production of Brilacidin.step c below
c) adding the compound of Formula II and pyrimidine-4,6-dicarboxylic acid in presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiirnide hydrochloride pyridine to form a compound of Formula III
The biochemists in the group may find it easier to follow process of assembly with the graphs listed in the link to the patent. Preceding this in the patent is a detailed outline of the immunologic properties of Brilacidin which have not been published.
GLTA,
Farrell
https://patents.google.com/patent/WO2016133733A1/en
DETAILED DESCRIPTION OF THE INVENTION
The starting materials, which are required to prepare the compound brilacidin and the pharmaceutically acceptable salts thereof, are commercially available in bulk. The compound brilacidin and the salts are prepared by
a) reacting (R)-(-)-N-Boc-3-pyrrolidinol with 2-chloro-5-(trifluoromethyl)-l ,3- dinitrobenzene in the presence of potassium ter-butoxide to form a compound having Formula I
Figure imgf000012_0001
I;
b) reacting the compound of Formula I with an alcohol and a transition metal catalyst in the presence of hydrogen to form a com ound of Formula II
Figure imgf000012_0002
?;
c) adding the compound of Formula II and pyrimidine-4,6-dicarboxylic acid in presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiirnide hydrochloride pyridine to form a compound of Formula III
Figure imgf000012_0003
in;
d) reacting the compound of Formula III with 5-(carbobenzoxyamino)valeric acid to form a compound of Formula IV
Figure imgf000012_0004
e) reducing the resultant compound of formula IV in the presence of an alcohol, a transition metal catalyst, and hydrogen to afford formula V
Figure imgf000013_0001
V;
f) reacting the resultant compound of V with di-N-Boc pyrazole in the presence of base to provide compound of formula VI ;
Figure imgf000013_0002
VI; and
deprotecting the compound of Formula VI using acid to produce PMX-30063 (brilacidin); and, if desired, preparing a pharmaceutically acceptable salt.
c) adding the compound of Formula II and pyrimidine-4,6-dicarboxylic acid in presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiirnide hydrochloride pyridine to form a compound of Formula III
The biochemists in the group may find it easier to follow process of assembly with the graphs listed in the link to the patent. Preceding this in the patent is a detailed outline of the immunologic properties of Brilacidin which have not been published.
GLTA,
Farrell
https://patents.google.com/patent/WO2016133733A1/en
DETAILED DESCRIPTION OF THE INVENTION
The starting materials, which are required to prepare the compound brilacidin and the pharmaceutically acceptable salts thereof, are commercially available in bulk. The compound brilacidin and the salts are prepared by
a) reacting (R)-(-)-N-Boc-3-pyrrolidinol with 2-chloro-5-(trifluoromethyl)-l ,3- dinitrobenzene in the presence of potassium ter-butoxide to form a compound having Formula I
Figure imgf000012_0001
I;
b) reacting the compound of Formula I with an alcohol and a transition metal catalyst in the presence of hydrogen to form a com ound of Formula II
Figure imgf000012_0002
?;
c) adding the compound of Formula II and pyrimidine-4,6-dicarboxylic acid in presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiirnide hydrochloride pyridine to form a compound of Formula III
Figure imgf000012_0003
in;
d) reacting the compound of Formula III with 5-(carbobenzoxyamino)valeric acid to form a compound of Formula IV
Figure imgf000012_0004
e) reducing the resultant compound of formula IV in the presence of an alcohol, a transition metal catalyst, and hydrogen to afford formula V
Figure imgf000013_0001
V;
f) reacting the resultant compound of V with di-N-Boc pyrazole in the presence of base to provide compound of formula VI ;
Figure imgf000013_0002
VI; and
deprotecting the compound of Formula VI using acid to produce PMX-30063 (brilacidin); and, if desired, preparing a pharmaceutically acceptable salt.
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