2,2,6,6-Tetramethylpiperidine → HCID 58075622, compound

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Reaction Steps

Synthesis of 2,4-dichloro-7-aryl-6,7-dihydro-5H-cyclopenta[d]pyrimidines 25 could also be performed according to the pathway described on Scheme 10. 4-Chloro-2,6-dimethoxypyrimidine 29 could be deprotonated with a strong base, such as n-butyllithium or 2,2,6,6-tetramethylpiperidine, and quenched with allyl bromide to give 5-allyl-4-chloro-2,6-dimethoxypyrimidine 30. Nencka, R.; Votruba, I.; H{hacek over (r)}ebabeck{grave over (y)}, H.; Jansa, P.; Tlou{hacek over (s)}t′ovà, E.; Horskà, K.; Masojìdkovà, M.; Hol{grave over (y)}, A. J. Med. Chem. 2007, 50, 6016-6023. The latter compound can react with α-styrylborinic acids in the presence of a palladium catalyst, such as tetrakis(triphenylphosphine)palladium, to provide compounds of formula 31 which can undergo ring closure olefine metathesis under Grubbs conditions to form 2,4-dimethoxy-7-aryl-5H-cyclopenta[d]pyrimidines 32. Grubbs, R. H. Handbook of Metathesis, 2003, First Edition, Wiley-VCH. The double bond in compounds 32 can be reduced to give 2,4-dimethoxy-7-aryl-6,7-dihydro-5H-cyclopenta[d]pyrimidines 33, which upon acid-catalyzed hydrolysis, followed by chlorination with phosphorus oxychloride afford intermediates 25.

Provenance & Evidence