Reductions nitro groups, palladium® acetate

Reduction of the nitro group to the amine 118 was achieved by hydrogenation over palladium on charcoal under moderate pressure. Again conversion to the final maleimide 119 was achieved by reacting the amine with maleic anhydride followed by cyclodehydration with acetic anhydride and triethylamine at room temperature. 

Indole derivatives have been prepared by reaction of 2-bromoanilines with enamines in the presence of palladium(II) acetate, reductive cyclization onto a nitro group d , or by the same type of cycloaddition that allows the synthesis of benzofuranols (see above) but using /j-quinone diimides . An example of an application of this latter method is the regioselective nucleophilic addition of 1-piperidino-l-propene (245) to the selectively activated Af -(phenylsulfonyl)-p-quinone diimide 244 (equation 51) °. Fur-... 

Selective reduction of the benzene ring in S, which contains a hindered nitro group, is possible over 30% palladium-on-carbon in acetic acid ° ... 

Reduction of aromatic nitro groups using triethylammonium formate, catalyzed by pal-ladium-on-carbon or a soluble triaryphosphine-palladium acetate catalyst is compatible with ester or amide functions, leading to a-amino esters . The nitro group of the pyra-none 2 is selectively reduced, without hydrogenolysis of the benzyl ether linkage in the presence of finely divided Ni ° ... 

The large scale cGMP synthesis of ABT-866 required reduction of the nitro group and hydrogenolysis of the acetate moiety of intermediate I. The palladium catalyzed hydrogenation of compound I was carefully studied in a systematic fashion for the effect of solvent, catalyst, pH, teirqierature, and concentration. Key to the success of our approach was the combination of rapid screening techniques and HPLC analysis. 

This is carried out by reduction with hydrogen in the presence of Pt02 (Adams catalyst) or palladium on a carrier (26) in ethanol. After filtering off the catalyst, the solution is worked up best by evaporating alcohol after the addition of acetic acid. The residue can be worked up immediately by acetylating it with acetic anhydride. The reduction of nitro groups takes place easily even in the case of dinitro compounds and nitrophenols. 

Compound 10b has been treated with a solution of the nitrating mixture made from acetic anhydride and nitric acid in dioxane affording nitro derivative 10c, with not very high yields. The catalytic reduction of nitro derivative 10c, carried out with hydrazine in ethanol in the presence of palladium on calcium carbonate, affords compound lOd. The guanidino group at C-5 has be i introduced by reaction of compound lOd with ( anamide in solution of hydrochloric acid affording the objective molecule 10. 

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