Interaction of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methyl-thieno[2,3-b]pyridine with Raney nickel

Abstract

3 Amino 2 (isoxazol 3 yl) 4 methoxymethyl 6 methylthieno[2,3 b]pyridine was synthesized by the reaction of 2(1H) thioxopyridine 3 carbonitrile with 3 chloromethylisoxazole in the pres ence of two equivalents of KOH. Boiling of 3 amino 2 (isoxazol 3 yl) 4 methoxymethyl 6 meth ylthieno[2,3 b]pyridine with Raney nickel results in 4 aminothieno[2,3 b;4,5 b´]dipyridine or 5 (4 amino 2 pyridyl)pyridine depending on the reaction conditions. Key words: 3 amino 2 (isoxazol 3 yl)thieno[2,3 b]pyridine, 4 aminothieno[2,3 b;4,5 b´] dipyridine, 5 (4 amino 2 pyridyl)pyridine, Raney nickel, hydrogenolysis, β enaminoaldehyde, desulfurization.It is well known that thieno[2,3 b]pyridines undergo reductive desulfurization upon treatment with Raney nickel. 1 Isoxazoles, under the same catalytic conditions, are easily subjected to hydrogenolysis of the N-O bond to β enaminoketones, which can undergo secondary cy clization reactions. 2-4 It was of interest to study the in teraction of Raney nickel with a compound containing thienopyridine and isoxazole fragments.3 Amino 2 (isoxazol 3 yl) 4 methoxymethyl 6 me thylthieno[2,3 b]pyridine (1) was taken as the subject of the investigation. It was synthesized (Scheme 1) by the reaction of 3 cyanopyridine 2(1Н) thione 2 with 3 chloromethylisoxazole (3) in the presence of 2 equiva lents of КОН according to the method analogous to that reported by us earlier. 5 It was shown that the interaction of 3 amino 2 (isox azol 3 yl)thieno[2,3 b]pyridine 1 with Raney nickel re sults in different products depending on conditions (Scheme 2). Thus 4 amino 9 methoxymethyl 7 meth ylthieno[2,3 b;4,5 b´]dipyridine (4) was formed upon refluxing of compound 1 with 10 equivalents of Raney nickel in ethanol-DMF (5 : 1) for 10 h. Evidently, hy drogenolysis of the N O bond of the isoxazole ring takes place with formation of β enaminoaldehyde 5 intramo lecular cyclization of which results in product 4.The reaction carried out in ethanol with 15 fold excess of Raney nickel for 30 h afforded 5 (4 amino 2 pyridi nyl) 4 methoxymethyl 2 methylpyridine (6) in 48% yield. It was shown by TLC that 4 aminothieno[2,3 b;4,5 b´]dipyridine 4 initially formed in the reaction mix ture undergoes reductive desulfurization resulting in com pound 6. Experimental IR spectra were recorded on a Specord IR 75 spectrophotometer in Nuiol. 1 Н NMR spectra were measured on a Bruker DRX 500 instrument (500.13 МHz) in DMSO d 6 , internal standart Me 4 Si. Mass spectra were recorded on a Varian CH 6 spectrometer (EI, 70 eV). Melting points were determined on a Boetius heating table and are uncorrected. Preparative chromatography was performed on the Sorbpolimer silica gel 50-160 µm. Scheme 1

Desulfurization of pyrido[3′,2′:4,5]thieno-[2,3-f]pyrrolo[1,2-a][1,4]diazepines

“…It is known [2][3][4] that the thiophene ring in a thienopyridine fragment can readily undergo desulfurization with opening of the thiophene ring. In this work we report results of a study of the condensed pyrrolodiazepines transformation which contain a thieno [2,3-b]pyridine fragment.…”