- Direct metalation of heteroaromatic esters and nitriles using a mixed lithium-cadmium base. Subsequent conversion to dipyridopyrimidinones
-
(Chemical Equation Presented) All pyridine nitriles and esters were metalated at the position next to the directing group using (TMP) 3CdLi in tetrahydrofuran at room temperature. The 2-, 3-, and 4-cyanopyridines were treated with 0.5 equiv of base for 2 h to afford, after subsequent trapping with iodine, the corresponding 3-iodo, 2-iodo, and 3-iodo derivatives, respectively, in yields ranging from 30 to 61%. Cyanopyrazine was similarly functionalized at the 3 position in 43% yield. Ethyl 3-iodopicolinate and -isonicotinate were synthesized from the corresponding pyridine esters in 58 and 65% yield. Less stable ethyl 4-iodonicotinate also formed under the same conditions and was directly converted to ethyl 4-(pyrazol-1-yl)nicotinate in a two-step 38% yield. All three ethyl iodopyridinecarboxylates were involved in a one-pot palladium-catalyzed cross-coupling reaction/cyclization using 2-aminopyridine to afford new dipyrido[1,2-a:3′,2′-d]pyrimidin-11- one, dipyrido[1,2-a:4′,3′-d]pyrimidin-11-one, and dipyrido[1,2-a:3′,4′-d]pyrimidin-5-one in yields ranging from 50 to 62%. A similar crosscoupling/ cyclization sequence was applied to methyl 2-chloronicotinate using 2-aminopyridine, 2-amino-5-methylpyridine, and 1-aminoisoquinoline to give the corresponding tricyclic or tetracyclic compounds in 43-79% yield. Dipyrido[1,2-a:4′,3′-d]pyrimidin-11-one and dipyrido[1,2-a:3′,4′-d]pyrimidin-5-one showed a good bactericidal activity against Pseudomonas aeroginosa. Dipyrido-[1,2-a:2′,3′-d] pyrimidin-5-one and pyrido[2′,3′:4,5]pyrimidino[2,1-a]isoquinolin-8- one showed a fungicidal activity against Fusarium and dipyrido[1,2-a:4′, 3′-d]pyrimidin-11-one against Candida albicans. Ethyl 4-(pyrazol-1-yl) nicotinate and dipyrido[1,2-a:2′,3′-d]pyrimidin-5-one have promising cytotoxic activities, the former toward a liver carcinoma cell line (HEPG2) and the latter toward a human breast carcinoma cell line (MCF7).
- Bentabed-Ababsa, Ghenia,Ely, Sidaty Cheikh Sid,Hesse, Stephanie,Nassar, Ekhlass,Chevallier, Floris,Nguyen, Tan Tai,Derdour, Aicha,Mongin, Florence
-
experimental part
p. 839 - 847
(2010/08/20)
-
- Carbopalladation of nitriles: Synthesis of 2,3-diarylindenones and polycyclic aromatic ketones by the Pd-catalyzed annulation of alkynes and bicyclic alkenes by 2-iodoarenenitriles
-
2-Iodobenzonitrile, its derivatives, and various heterocyclic analogues undergo palladium(O)-catalyzed annulation onto diarylacetylenes or bicyclic alkenes to afford 2,3-diarylindenones and polycyclic aromatic ketones in very good to excellent yields. This reaction represents one of the first examples of the addition of an organopalladium moiety to the carbon-nitrogen triple bond of a nitrile. The reaction is compatible with a number of functional groups. A reaction mechanism, as well as a model accounting for the electronic effects of substituents on the aromatic ring of the nitrile, is proposed.
- Pletnev, Alexandre A.,Tian, Qingping,Larock, Richard C.
-
p. 9276 - 9287
(2007/10/03)
-
