A new synthesis of N‐alkyl pyrazolidine‐3,5‐diones and tetrahydropyridazine‐3,6‐diones

Abstract

N‐alkyl pyrazolidine‐3,5‐diones and tetrahydropyridazine‐3,6‐diones have been synthesized by a new method in a three‐step sequence from dialkyl malonates or succinates respectively.

Comparison of 3D Structures and AT1 Binding Properties of Pyrazolidine-3,5-diones and Tetrahydropyridazine-3,6-diones with Parent Antihypertensive Drug Irbesartan

“…6,8 General Procedure for Alkylation of Compound 4 and 7. K2CO3 (5.3 mmol) was added portion wise to a solution of compounds 4 or 7 16 (1.78 mmol) in DMF (30 mL). The desired alkyl bromide 5 (or 8) (1.78 mmol) was then added to the reaction mixture, which was allowed to stir for 20 h at room temperature.…”

“…The synthesis of regioisomers 2 and 3 is outlined in Schemes 1 and 2, respectively. Alkylation of N-butyltetrahydropyridazine-3,6-dione 4 16 with N-triphenyl-5-[4′-(bromomethyl)biphenyl-2-yl]tetrazole 5 in dimethylformamide (DMF) in the presence of potassium carbonate afforded the desired N-alkylated product 6. The trityl group of 6 was subsequently cleaved by treatment with HCl in water/tetrahydrofuran (THF) to yield the target compound 2 in good yield.…”

“…The trityl group of 6 was subsequently cleaved by treatment with HCl in water/tetrahydrofuran (THF) to yield the target compound 2 in good yield. Compound 3 was obtained from N-butyltetrahydropyridazine-3,6-dione 7 16 (regioisomer of 4) by alkylation with 4-(bromomethyl)-2′cyanobiphenyl 8 followed by formation of the tetrazole ring with tributyltin azide in DMF.…”