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A novel synthetic route to 7-substituted derivatives of the antitumor agent LY231514 (MTA)

โœ Scribed by Edward C. Taylor; Bin Liu

Publisher
Elsevier Science
Year
1999
Tongue
French
Weight
230 KB
Volume
40
Category
Article
ISSN
0040-4039

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โœฆ Synopsis

This paper describes a further synthesis of the pyrrolo [2,3-d]pyrimidine antitumor agent MTA (LY231514). Manganie triacetate dihydrate-induced radical cyclization of methyl N-crotyl-N-(3',4'dimethoxybenzyl)malonamide (4d) yielded the 3-carbomethoxy-2-pyrrolidinone 5d that was then thiated with P2S5 to the corresponding thiolactam (6d). Cyclization with guanidine gave the 7-substituted 2-amino-4(3H)oxo-5,6-dihydro-pyrrolo[2,3-d]pyrimidine (7d). Pd-catalyzed coupling with diethyl 4-iodobenzoylglutamate yielded (in a single step) the diethyl ester 9d. Deprotection with H2SO4/TFA followed by saponification then gave MTA. Several additional 7-substituted derivatives of MTA were prepared by use of this methodology. In contradiction to a published claim, these 7-substituted derivatives proved to be devoid of any significant cell growth inhibitory activity.

๐Ÿ“œ SIMILAR VOLUMES

Michael addition of ethyl acetoacetate t
Michael addition of ethyl acetoacetate to ฮฑ,ฮฒ-unsaturated oximes in the presence of FeCl3: a novel synthetic route to substituted nicotinic acid derivatives
โœ Andrey M Chibiryaev; Norbert De Kimpe; Alexey V Tkachev ๐Ÿ“‚ Article ๐Ÿ“… 2000 ๐Ÿ› Elsevier Science ๐ŸŒ French โš– 69 KB

The FeCl 3 -catalyzed reaction of a,b-unsaturated oximes with ethyl acetoacetate resulted in Michael addition followed by ring closure to produce substituted nicotinic acid derivatives in a very efficient way.