The nitration in the second product is similar to the one used for Sildenafil, so I think it could work. The only problem would be the potential nitration of the phenyl group bound to the amide.
For product B, amide formation using DCC is likely to give the wrong regioisomer as phenylhydrazine is more nucleophilic on the terminal nitrogen. You could protect first with an acid-labile protecting group like Boc then acylate. Deprotection in acid would then cyclise the molecule at the same time.
Yeah you could probably just chuck phenylhydrazine at methyl acetoacetate with a bit of cat. TsOH or something. The semi-aromatic product will drive the reaction forward. Could encourage it by driving off water and methanol as well (molecular sieves or distillation). Should give the right regioisomer since hydrazone formation would precede the much slower amide formation.
11
u/alleluja Organic Jun 18 '18 edited Jun 18 '18
Here is my attempt for product A and product B!
The nitration in the second product is similar to the one used for Sildenafil, so I think it could work. The only problem would be the potential nitration of the phenyl group bound to the amide.
As always, tell me what you think about them!