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Synthesis of [ 3 H]CI‐980, ethyl[5‐anino‐1,2‐dihydro‐2( S )‐methyl‐3(3‐[ 3 H]phenyl)pyrido[3,4‐ b ]jpyrazin‐7‐YL] carbamate isethionate salt, a tubulin‐binding, antimitotic, broad‐spectrum antitumor agent
Author(s) -
Lee Helen T.,
Woo Peter W. K.
Publication year - 1994
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580340103
Subject(s) - chemistry , medicinal chemistry , yield (engineering) , hydrogenolysis , sodium borohydride , acetic acid , ketone , nitrile , chromium trioxide , catalysis , organic chemistry , chromium , materials science , metallurgy
[ 3 H]CI‐980 ( 10b ) was synthesized in an eight‐step sequence with an overall yield of 2.4%. Reaction of m ‐bromophenyl lithium ( 2 ) with N ‐ethoxycarbonyl‐L‐alanine gave the chiral ketone 3 . Reduction of 3 with sodium borohydride followed by alkaline N ‐deprotection and condensation with ethyl 6 ‐amino‐ 4 ‐chloro‐ 5 ‐nitro‐ 2 ‐pyridine carbamate ( 6 ) gave 7 . Chromium trioxide oxidation of 7 followed by reductive cyclization with iron‐acetic acid gave the key bromo intermediate 9 . Palladium catalyzed 3 H‐hydrogenolysis of 9 gave the free base form of [ 3 H]CI‐980 ( 10a ), which was converted to the isethionate salt ( 10b ) before use.