Octahydro-2,6-naphthyridine

Nitrosation of iranj-decahydro-1,8-naphthyridine (67) gives the dinitroso derivative (18) (84JOC1481). The octahydro-1,8-naphthyridine (68) gives the methyl derivative (69) (75% yield)... 

Cruz, D., Wang, Z., Kibbie, J., Modlin, R., and Kwon, O. (2011). Diversity through phosphine catalysis identifies octahydro-l,6-naphthyridin-4-ones as activators of endothelium-driven immunity. Proc Natl Acad Sci USA 108 6769-6774. 

Cyclization of the anilide of 3-(2-hydroxyethyl)pyridine-2-carboxylic acid occurred under the action of diethyl azodicarboxylate and Ph3P. Subsequent treatment of the resulting 2,6-naphthyridine 126 with phenacyl bromide and then with sodium borohydride afforded octahydro-2,6-naphtyridine 127 covered by a patent as a medicine for prophylaxis and treatment of schizophrenia and depressions (1997BRP2299582). 

C1oH9BrN202 r 8a-Bromo-1,2,3,5,6,7,8,8a-octahydro-1,3-dioxoisoquino-line-4-carbonitrile, 41B, 319 C10H9N, 3-Methylisoquinoline, 40B, 245 C10H9NO2, 3-Indolylacetic acid, 29, 726 C1oH10N2O2 f 4,8-Dimethoxy-1,5-naphthyridine, 43B, 330 C10H10N2O3, N-Ethanol- -isatoxime, 39B, 195... 

Based on the bicyclic structure of the octahydro-1,6-naphthyridin-4-one 92, a chemical library was prepared by employing a solid-phase synthesis technique and evaluated by an EC activation assay that measured the production of macrophage inflammatory protein 1 beta (MIPljS), a marker of EC activation by IFNy. Reaction conditions were first established by using SynPhase lanterns as solid supports. Allenoate 93 was subjected to a phosphine-catalyzed [4 + 2] annulation reaction with A-tosylbenzaldimine 94. 

The resulting tetrahydropyridine 95 was then converted into dienol ether 96 using a Tebbe reagent. A subsequent e Jo-selective Diels-Alder reaction with A-tosylbenzaldi-mine 94 produced octahydro-l,6-naphthyridin-4-ones 97a,b with a diastereomeric ratio of 97 3 (Scheme 16.14). ... 

SCHEME 16.14. Solid-phase synthesis of octahydro-l,6-naphthyridin-4-ones. Academy of Sciences. AU rights reserved. 

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