Originator
Ubretid,Hormonchemie,W. Germany,1966
Definition
ChEBI: Distigmine bromide is an organic bromide salt of distigmine. It is an anticholinesterase drug used for the treatment of myasthenia gravis and postoperative urinary retention. It has a role as an EC 3.1.1.8 (cholinesterase) inhibitor. It is a pyridinium salt and an organic bromide salt. It contains a distigmine.
Manufacturing Process
2 parts of sodium are dissolved in 24 parts of methanol and to the solution of
sodium methylate formed 8.25 parts of 3-oxypyridine and 90 parts of xylene
(mixture of isomers) are added. Then the mixture is distilled in an atmosphere
of nitrogen as protecting gas until the boiling point of xylene is reached and
the methanol is completely removed. The remainder is brought together with
a solution of 11.7 parts of hexamethylene-bis-(N-methyl carbamic acid
chloride) in 45 parts of xylene and maintained 4 hours at a temperature of80°C under vigorous stirring.
After having been cooled it is washed three times in water, three times in a
5% solution of caustic soda, and then another three times in water. The
solution in xylene is dried over sodium sulfate and the xylene is completely
distilled off in vacuo. Thus 11.0 parts of hexamethylene-bis-(Nmethylcarbamic acid-3-pyridyl ester) are obtained.
7.3 parts of hexamethylene-bis-(N-methyl carbamic acid-3-pyridyl ester) are
dissolved in 120 parts of acetone, then 22 parts of methyl bromide are added
and the mixture is left to stand at room temperature until the reaction is
finished, whereby crystals are precipitated. The reaction product after being
drawn off and dried (9.9 parts) can be purified by dissolving in acetic acid and
precipitating with methyl ethyl ketone. The hexamethylene-bis-(N-methyl
carbamic acid-3-pyridyl ester bromomethylate) has a micro melting point
between 147°C and 150°C.
