Start Date
2019
Description
- Indolizines are a versatile heterocyclic core that occurs frequently in pharmaceutical leads for a variety of indications, including: anti-bacterial1 and anti-tumor agents,2 and targets for the treatment of Alzheimer’s disease,3 asthma,4 erectile dysfunction,5 and inflammation related to respiratory or cardiovascular disease.
- While evaluating the scope of a Au(I)-catalyzed rearrangement of 2- propargyloxypyridine 1, 7 substituted indolizine 4 was discovered as an unexpected by-product (Scheme 1). The structure of indolizine 4 was confirmed by NMR and Xray analysis. Investigations revealed that acetophenone, originally present as an impurity in the reaction, is a key reagent. The use of acetophenone as the solvent, in the presence of 1-phenylethanol (5 equiv), was determined to be optimal.
Recommended Citation
Hartgerink, Colin T.; De Burg, Jaimie E. Van; and Anderson, Carolyn E., "Synthesis of Trisubstituted Indolizines from 2-Propargyloxypyridines" (2019). Summer Research. 8.
https://digitalcommons.calvin.edu/summer_research/2019/Posters/8
COinS
Jan 1st, 12:00 AM
Synthesis of Trisubstituted Indolizines from 2-Propargyloxypyridines
- Indolizines are a versatile heterocyclic core that occurs frequently in pharmaceutical leads for a variety of indications, including: anti-bacterial1 and anti-tumor agents,2 and targets for the treatment of Alzheimer’s disease,3 asthma,4 erectile dysfunction,5 and inflammation related to respiratory or cardiovascular disease.
- While evaluating the scope of a Au(I)-catalyzed rearrangement of 2- propargyloxypyridine 1, 7 substituted indolizine 4 was discovered as an unexpected by-product (Scheme 1). The structure of indolizine 4 was confirmed by NMR and Xray analysis. Investigations revealed that acetophenone, originally present as an impurity in the reaction, is a key reagent. The use of acetophenone as the solvent, in the presence of 1-phenylethanol (5 equiv), was determined to be optimal.