4-Chlorothieno[2,3-b]pyridine-5-carbonitrile

The syntheses of the new thieno[2, 3-b]pyridine phosphoramidates conjugates (9a–c) were performed by nucleophilic aromatic substitution of the chlorine atomin 4-substituted thieno[2, 3-b]pyridine (5) by aminoalkylphosphoramidates 6a–c(Scheme 1). The starting 4-chlorothieno[2, 3-b]pyridine-5-carbonitrile 5 was prepared from 2-nitrothiophene 1, which was reduced with tin and hydrochloric acid, leading to the bis-(2-thienylammonium)hexachlorostannate 2. This compound was immediately condensed with ethyl (ethoxymethylene)cyanoacetate in pyridine at 40–50 C over a period of 24 h to produce ethyl a-cyano-b-(N-2-thienylammonium)acrylate 3 in88percent yield. The cyclization of the acrylate was carried out by refluxing in Dowthermat 250 C for 40 min, after which 4-hydroxythieno[2, 3-b]pyridine-5-carbonitrile 4 was isolated in 78percent yield, through precipitation from petroleum ether. Compound 4 was easily chlorinated refluxing phosphorus oxychloride at 110 C over a period of 6 h to afford 4-chlorothieno[2, 3-b]pyridine-5-carbonitrile 5 in 76percent yield.

Molecular Weight:194.64
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Exact Mass:193.9705470
Monoisotopic Mass:193.9705470
Topological Polar Surface Area:64.9
Heavy Atom Count:12
Complexity:224
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes