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Scheme 1 Pathways of RAD synthesis Scheme 2 Pathways of intermediate 9 synthesis.
Finally, the title compounds (10a 10x) were conveniently obtained in an >70% yield by treating of intermediate 9 with the corresponding acyl chloride in the presence of triethylamine in acetone or acetonitrile.
It is believed that also in this case, the acyclic intermediate 4 was formed and then cyclized via attack of the arylhydrazone moiety at CN to afford the pyridazine imine intermediate 9 that was hydrolyzed under the reaction conditions to yield the final isolable pyridazinone 10.
In the next step, intermediate 9 was linked with a carbazole moiety to generate derivatives KL022 KL035.
The synthetic pathways to make scaffolds 10 and 11 are described in Scheme 3. The key intermediate 9 was obtained in 4 steps with roughly 50% overall yield.
Intermediate 9 was obtained from reaction of aromatic or aliphatic amine with methanesulfonyl chloride followed by reaction with sodium hydride and epichlorohydrin.
Similar(42)
Expression of gliZ was increased in expression in wild-type, along with gliP, the bimodular non-ribosomal peptide synthetase that produces the cyclo-L-Phe-L-Ser diketopiperazine intermediate [ 9, 10, 43].
DNCE BC2248 Jazz, II: Intermediate. 1 point.
DNCE BC2447 Tap, II: Intermediate. 1 point.
We use the UVic Earth System Model of Intermediate Complexity21.
DNCE BC2139 Ballet, IV: High Intermediate. 1 point.
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