Event Title
Synthesis of (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (S2): A Precursor to Selective Bromodomain Inhibitor, (+)-JQ1
Faculty Sponsor
Elizabeth J.O. Atkinson
Location
Jereld R. Nicholson Library
Date
5-17-2013 3:00 PM
End Date
5-17-2013 4:30 PM
Subject Area
Chemistry
Description
S2 [(2-amino-4,5-dimethylthiophen-3-yl)(4-chloropheyl)methanone)] is an organic precursor to the (+)-enantiomer of JQ1, a break-through molecule in cancer research. The purpose of this research was to sufficiently synthesize enough of the S2 intermediate to continue the synthetic pathway of (+)-JQ1. The synthesis of S2 is similar to the Gewald reaction, where 2-butanone (ketone) condenses 4-chlorobenzoylacetonitrile (α-cyanoester) in the presence of elemental sulfur and morpholine (base) to yield the poly-substituted thiophene product, though the mechanism for the cyclization is still unknown. The resulting residue was characterized by thin-layer chromatography and purified using column chromatography. The greatest yield of S2 resulted from recrystallization with ethanol/water. Proton NMR of the product was compared to that of theoretical research done by fellow Linfield student Kevin Romero. Now that S2 has successfully been synthesized, we will begin the next step in the synthesis of (+)-JQ1.
Recommended Citation
Hillyer, Jake T. and Scheafer, David R., "Synthesis of (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (S2): A Precursor to Selective Bromodomain Inhibitor, (+)-JQ1" (2013). Science and Social Sciences. Event. Submission 37.
https://digitalcommons.linfield.edu/studsymp_sci/2013/all/37
Synthesis of (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (S2): A Precursor to Selective Bromodomain Inhibitor, (+)-JQ1
Jereld R. Nicholson Library
S2 [(2-amino-4,5-dimethylthiophen-3-yl)(4-chloropheyl)methanone)] is an organic precursor to the (+)-enantiomer of JQ1, a break-through molecule in cancer research. The purpose of this research was to sufficiently synthesize enough of the S2 intermediate to continue the synthetic pathway of (+)-JQ1. The synthesis of S2 is similar to the Gewald reaction, where 2-butanone (ketone) condenses 4-chlorobenzoylacetonitrile (α-cyanoester) in the presence of elemental sulfur and morpholine (base) to yield the poly-substituted thiophene product, though the mechanism for the cyclization is still unknown. The resulting residue was characterized by thin-layer chromatography and purified using column chromatography. The greatest yield of S2 resulted from recrystallization with ethanol/water. Proton NMR of the product was compared to that of theoretical research done by fellow Linfield student Kevin Romero. Now that S2 has successfully been synthesized, we will begin the next step in the synthesis of (+)-JQ1.