3- Methyl 4 nitropyridine 1-oxide synthesis

Tile same methodology as mentioned for the preparation of (9) was applied for the synthesis of 8-nitro-l,6-naphthyridines. Heating diethyl N- 3-nitropyridin-4-yl)aminomethylenemalonate (12) in diphenyl ether yields ethyl 8-nitro-l,6-naphthyridin-4(lH)-one 3-carboxylate (13) (63JCS4237, 30%) and acid treatment of 4-( y, y-diethoxypropylamino)-5-nitro-2-(/3,/3 -trifluoroethoxy)-pyridine (14) gives in a similar way 8-nitro-5-(/3, /3-triflu-oroethoxy)-l,2-dihydro-l,6-naphthyridine (15, 76%). Subsequent oxidation with chloranil, acid hydrolysis, and methylation with methyl iodide gives 8-nitro-6-methyl-l,6-naphthyridin-5(6H)-one (16,63%) (81JHC941). 

Having established that the end game of the proposed synthesis of cylindrospermopsin (1) from bromoketone 4 was viable, we turned our attention to the preparation of acetylene 5 from 4-methoxy-3-methylpyridine (7). 4-Methoxy-3-methylpyridine (7) was prepared by modifications of the literature procedure.17,18 3-Methyl-4-nitropyridine A-oxide (27),19 was treated with K2CO3 in methanol at 70 °C to displace the nitro group to... 

Preparation of the 2-chloro-3-methoxy-4-nitropyridine A -oxide intermediate in the synthesis was considerably improved by the methylation of commercially available 2-chloro-3-pyridinol using dimethylsulfate and tet-rabutylammonium bromide as the catalyst under phase-transfer conditions (370), instead of diazomethane (Scheme 48). In the synthesis of orellanines elaborated by Tiecco et al. (299,301,309), shown in Scheme 49, the commercially available 3-hydroxypyridine was the starting material. The structures of the synthetic compounds were proved to be identical to those... 

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