Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Apr 9;14(4):268-72.
doi: 10.1021/co2001839. Epub 2012 Mar 5.

Facile (triazolyl)methylation of MACOS-derived benzofused sultams utilizing ROMP-derived OTP reagents

Saqib Faisal  1 , Farman Ullah, Pradip K Maity, Alan Rolfe, Thiwanka B Samarakoon, Patrick Porubsky, Benjamin Neuenswander, Gerald H Lushington, Fatima Z Basha, Michael G Organ, Paul R Hanson
Affiliations

Facile (triazolyl)methylation of MACOS-derived benzofused sultams utilizing ROMP-derived OTP reagents

Saqib Faisal et al. ACS Comb Sci. .

Abstract

A combination of MACOS scale-out and ROMP-derived oligomeric triazole phosphates (OTP(n)) have been successfully utilized for the preparation of a 106-member library of triazole containing benzothiaoxazepine-1,1-dioxides. This report demonstrates the utilization of a suite of soluble OTP(n) reagents for facile (triazolyl)methylation of 10 MACOS-derived sultam scaffolds in purification-free process for parallel synthesis of small molecule collections for HTS.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Scaffolds (1-10) and OTP20 Reagents {1–14} Library Building Blocks.
Scheme 1
Scheme 1
Facile Library Generation Utilizing MACOS Scale-out Sultam Scaffolds and ROMP-derived OTPn Reagents.
Graph 1
Graph 1
Final Mass, Purity and Yield Analysis for Benzothiaoxazepine-1,1-dioxide Library.
Graph 1
Graph 1
Final Mass, Purity and Yield Analysis for Benzothiaoxazepine-1,1-dioxide Library.
See this image and copyright information in PMC

References

    1. Dolle RE, Bourdonnec BL, Worm K, Morales GA, Thomas CJ, Zhang W. Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2009. J Comb Chem. 2010;12:765–806. - PMC - PubMed
    2. Dolle RE, Bourdonnec BL, Goodman AJ, Morales GA, Thomas CJ, Zhang W. Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2008. J Comb Chem. 2009;11:739–790. - PubMed
    3. Dolle RE, Bourdonnec BL, Goodman AJ, Morales GA, Thomas CJ, Zhang W. Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2007. J Comb Chem. 2008;10:753–802. - PubMed
    1. Bonander N, Bill RM. Relieving the first bottleneck in the drug discovery pipeline: Using array technologies to rationalize membrane protein production. Expert Rev Proteomics. 2009;6:501–505. - PubMed
    2. Seeberger PH. Organic Synthesis Scavengers in full flow. Nat Chem. 2009;1:258–260. - PubMed
    1. Gershell LJ, Atkins JH. A brief history of novel drug discovery technologies. Nature Rev Drug Discov. 2003;2:321–327. - PubMed
    2. Kappe CO, Dallinger D. The Impact of Microwave Synthesis on Drug Discovery. Nature Rev Drug Discov. 2006;5:51–63. - PubMed
    3. O’Brien M, Denton R, Ley SV. Lesser-Known Enabling Technologies for Organic Synthesis. Synthesis. 2011;8:1157–1192.
    4. Hanson PR, Samarakoon T, Rolfe A. In: The Power of Functional Resins in Organic Synthesis. Albericio F, Tulla-Puche J, editors. Wiley-VCH; Weinheim, Germany: 2008.
    5. Kappe CO, Dallinger D. Controlled Microwave Heating in Modern Organic Synthesis. Highlights from the 2004–2008 Literature. Mol Diversity. 2009;13:71–193. - PubMed
    1. Wirth T, editor. Microreactors in Organic Synthesis and Catalysis. Wiley-VCH; Weinheim: 2008.
    2. Yoshida J. Flash Chemistry. Wiley; Chichester: 2008.
    3. Baumann M, Baxendale IR, Kuratli C, Ley SV, Martin RE, Schneider J. Synthesis of a Drug-Like Focused Library of Trisubstituted Pyrrolidines Using Integrated Flow Chemistry and Batch Methods. ACS Combi Sci. 2011;13:405–413. - PubMed
    4. Roberge DM, Zimmermann B, Rainone F, Gottsponer M, Eyholzer M, Kockmann N. Microreactor Technology and Continuous Processes in the Fine Chemical and Pharmaceutical Industry: Is the Revolution Underway. Org Process Res Dev. 2008;12:905–910.
    5. Wiles C, Watts P. Improving Chemical Synthesis Using Flow Reactors. Expert Opinion on Drug Discovery. 2007;2:1487–1503. - PubMed
    1. Carter CF, Baxendale IR, Pavey JBJ, Ley SV. The continuous flow synthesis of butane-2,3-diacetal protected building blocks using microreactors. Org Biomol Chem. 2010;8:1588–1595. - PubMed
    2. Wiles C, Watts P, Haswell SJ. The use of solid-supported reagents for the multi-step synthesis of a combinatorial array of analytically pure alpha, beta-unsaturated compounds in miniaturized flow reactors. Lab Chip. 2007;7:322–330. - PubMed

Publication types