Water → 1-(2,1,3-benzothiadiazol-5-yl)-3-[3-(pyridin-4-yl)propyl]-1,8-naphthyridin-2(1H)-one

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Reaction Steps

Ethyl 5-(pyridin-4-yl)pentanoate (1.5 eq., prepared in Synthetic Example 2) was dissolved in dry THF. To the solution was added LDA (2M solution, 1.5 eq.) at −78° C. or below in a dry ice-methanol bath under nitrogen atmosphere while stirring and the mixture was stirred for 1 hour. Next, to the reaction mixture was added dropwise a solution of 2-(2,1,3-benzothiadiazol-5-ylamino)-nicotinaldehyde (1.0 eq., prepared in Synthetic Example 1a)) in THF and the resultant mixture was stirred for 2 hours at −78° C. and then continued to stir for 24 hours until it reached room temperature. The reaction mixture was treated with water, and extracted with methylene chloride. The extract was dried, and evaporated. To the residue was added ethyl acetate to form crystals. Thus, 1-(2,1,3-benzothiadiazol-5-yl) -3-[3-(pyridin-4-yl)propyl]-1,8-naphthyridin-2(1H)-one was obtained. The product was purified through flash column chromatography and recrystallization (yield: 43%, mp 193.5–195.5° C./DMF).

Provenance & Evidence