ChemicalBook CAS DataBase List Thieno[3,2-b]pyridine-6-carbonitrile (9CI)

Thieno[3,2-b]pyridine-6-carbonitrile (9CI) synthesis

5synthesis methods

Product Name:Thieno[3,2-b]pyridine-6-carbonitrile (9CI)
CAS Number:116538-95-5
Molecular formula:C8H4N2S
Molecular Weight:160.2

17721-06-1
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105161-33-9 Synthesis

3,3-Dimethoxy-2-(hydroxymethylene)propionitrile sodium salt

105161-33-9
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Thieno[3,2-b]pyridine-6-carbonitrile (9CI)

116538-95-5
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Yield:116538-95-5 93%

Reaction Conditions:

Stage #1: 3-aminothiophene;3,3-dimethyloxy-2-formylpropionitrile sodium saltwith hydrogenchloride in methanol;water at 20; for 4 h;
Stage #2: with hydrogenchloride in methanol;water at 20; for 12 h;Solvent;Temperature;Time;

Steps:

General Procedure for the Formation of 4 and 5 by the Cyclizationof Aminoheterocycles 1 and 2 with 3,3-Dimethoxy-2-formylpropionitrileSodium Salt 3

General procedure: Salt 3 (6 mmol) was dissolved in MeOH (3 mL), then the concentratedaqueous solution of HCl (0.5 mL) and 1 or 2 (5 mmol) in MeOH (5 mL)were added. The reaction mixture was stirred for 4 h at r.t. After this,the additional MeOH (2 mL) and HCl (1.5 mL) were added. The reaction mixture was additionally stirred for 12 h at r.t. Then the saturatedsolution of NaHCO3 was added dropwise to the reaction mixtureuntil pH 7-8. After this, the target compound was extracted by CHCl3(3 × 30 mL). The organic layers were separated, combined, and driedover Na2SO4. The solvent was removed by evaporation under reducedpressure. The product was purified by preparative gradient chromatographyon silica gel with 10% EtOAc in hexane. The compounds 4 or5 were obtained as white powders. Yields, melting points, and LCMSdata are given in Table 2. NMR data and Rf (for chromatographic purificationusing 10% EtOAc in hexane) are given below.

References:

Mityuk, Andrey P.;Hrebonkin, Andrii;Lebed, Pavlo S.;Grabchuk, Galyna P.;Volochnyuk, Dmitriy M.;Ryabukhin, Sergey V. [Synthesis,2021,vol. 53,# 12,p. 2133 - 2141]