Am I even close to solve this problem or it is a complete disaster?

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    $\begingroup$ For one thing, to make a diazonium salt with NaNO2/HCl you need an amino group on the aromatic ring. Perhaps only a partial disaster. ;) Oh yes, welcome to ChemSE! $\endgroup$ – user55119 Sep 23 '20 at 2:28
  • $\begingroup$ @Frederico I think it would help you to look up the reactions of 2-halopyridines with nucleophiles $\endgroup$ – Waylander Sep 23 '20 at 6:31
  • $\begingroup$ Out of curiosity: The scheme suggests a C-N coupling reaction between 1,8-diazanaphthalene and an aryldiazonium salt. May someone indicate the name for this type of reaction or / and a literature example for such a transformation? $\endgroup$ – Buttonwood Sep 23 '20 at 12:34
  • $\begingroup$ Photoarylation of pyridine with an aryl diazonium salt at all positions of pyridine has been reported: DOI:10.1021/acs.joc.9b0187 Can't speak to the suggestion by the OP. @Buttonwood $\endgroup$ – user55119 Sep 23 '20 at 15:54
  • $\begingroup$ @user55119 Perhaps we are not on the same page, do you refer to Bartomoleu, 2019JOC10459 (doi 10.1021/acs.joc.9b01879) -- as the last figure was truncated? Scheme 2 of the paper and the NMR of the 88 p. SI read like pyridines / quinolines / quinoxalines underwent C-H arylation at 2, or / and 4 position relative to N, but no NMR record evidence of a C-N bond formation with what was a pyridine-N. But even if there was a misunderstanding here, good to know about this photo mediated approach, since one of rules of retrosynthesis is «the strategy is better if a similar reaction already was seen». $\endgroup$ – Buttonwood Sep 23 '20 at 18:18

Here is a possible route: Start from the commercially available 2,6-dichloro-5-fluoropyridine-3-carboxylic acid (1). Form the Weinreb amide (2) via the acid chloride. React this with vinyl magnesium bromide to form (3). React the product with 1 eq of aniline in the presence of non-nucleophilic base to produce (4). Isolate this product and react with excess piperazine for the final product (5).

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    $\begingroup$ The closest analogue found by ChemSpider is this one : chemspider.com/… ; I wonder if that keto ester could help with the synthesis and be removed at the end by hydrolysis and decarboxylation. $\endgroup$ – user6376297 Sep 23 '20 at 17:27
  • $\begingroup$ Yes, I think the hydrolysis and decarboxylation would deliver the desired structure. The difference would come down to the yields in installing the vinyl ketone v the methylene beta keto-ester $\endgroup$ – Waylander Sep 23 '20 at 17:42
  • $\begingroup$ I was thinking more of installing that C-C moiety the other way around. Suppose you start from an ester of your (1), do the substitution of the 2-Cl with the aniline, then a Michael addition to an acrylate and an intramolecular acylation (Dieckmann?). Just to avoid harsh nucleophylic conditions on such an electrophylic molecule. But yes, your route seems more direct. $\endgroup$ – user6376297 Sep 23 '20 at 19:02
  • $\begingroup$ user6376297: The Dieckmann route has been applied in this series of cmpds. T. Miyamoto, H. Egawa and j. Matsumoto, Chem. Pharm. Bull., 1987, 35, 2280. $\endgroup$ – user55119 Sep 23 '20 at 19:23
  • $\begingroup$ This discussion illustrates very clearly that there is rarely only a single potential route to a target $\endgroup$ – Waylander Sep 23 '20 at 19:30

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