Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Download PDF
Synthesis 2020; 52(01): 105-118
DOI: 10.1055/s-0037-1610734
DOI: 10.1055/s-0037-1610734
paper
Regiocontrolled Synthesis of 6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazines
Further Information
Publication History
Received: 27 August 2019
Accepted after revision: 17 September 2019
Publication Date:
08 October 2019 (online)
Abstract
Synthetic access to 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazines has been achieved in 3–4 steps from commercially available pyrazoles. Optimization of a protected hydroxyethyl group on N1 enabled the regiocontrolled construction of pyrazole-5-aldehydes in high yields; subsequent deprotection and reduction generated fused heterocyclic scaffolds bearing multiple substitution patterns. Moreover, the intermediate pyrazole lactols were shown to be versatile synthetic building blocks.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610734.
- Supporting Information
-
References
- 1 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
- 2 Pennington LD, Moustakas DT. J. Med. Chem. 2017; 60: 3552
- 3 Delost MD, Smith DT, Anderson BJ, Njardarson JT. J. Med. Chem. 2018; 61: 10996
- 4a Velaparthi U, Kumaravel S, Karuppiah AM. S. S, Maheshwarappa SH, Rachamreddy CR, Wittman MD. WO Patent 2015195880, 2015
- 4b Stansfield I, Querolle OA. G, Ligny YA. E, Gross GM, Jacoby E, Meerpoel L, Green SR, Hynd G, Kulagowski JJ, Macleod C, Mann SE. WO Patent 2018002219, 2018
- 4c Patel S, Hamilton G. WO Patent 2018109097, 2018
- 4d Estrada AA, Chan BK, Baker-Glenn C, Beresford A, Burdick DJ, Chambers M, Chen H, Dominguez SL, Dotson J, Drummond J, Flagella M, Fuji R, Gill A, Halladay J, Harris SF, Heffron TP, Kleinheinz T, Lee DW, Le PichonC. E, Liu X, Lyssikatos JP, Medhurst AD, Moffat JG, Nash K, Scearce-Levie K, Sheng Z, Shore DG, Wong S, Zhang S, Zhang X, Zhu H, Sweeney ZK. J. Med. Chem. 2014; 57: 921
- 4e Baker-Glenn C, Chan BK, Dotson J, Estrada A, Heffron T, Lyssikatos J, Sweeney ZK. WO Patent 2013164323, 2013
- 4f Crawford JJ, Ortwine DF, Wei B, Young WB. US Patent Appl. 2013116246, 2013
- 4g Friedman MM, Cox P, Frank KE, Hoemann MZ, Osuma A, Wilson NS, Xu X. WO Patent 2015157955, 2015
- 4h Blomgren P, Currie KS, Kropf JE, Lee SH, Mitchell SA, Schmitt AC, Xu J, Zhao Z. WO Patent 2011112995, 2011
- 4i Barlaam B, De Savi C, Hawkins J, Hird A, Lamb M, Pike K, Vasbinder M. US Patent Appl. 20160376287, 2016
- 5a Venkatesan AM, Mansour TS, Abe T, Yamamura I, Takasaki T, Agarwal A, Santos OD, Sum F.-W, Lin Y.-I. WO Patent 2003093279, 2003
- 5b Venkatesan AM, Agarwal A, Abe T, Ushirogochi H, Yamamura I, Ado M, Tsuyoshi T, Santos OD, Gu Y, Sum F.-W, Li Z, Francisco G, Lin Y.-I, Petersen PJ, Yang Y, Kumagai T, Weiss WJ, Shlaes DM, Knox JR, Mansour TS. J. Med. Chem. 2006; 49: 4623
- 6 Mattes A, Helmke H, Hillebrand S, Peris G, Sudau A, Rodefeld L, Gauger S, Benting J, Dahmen P, Meissner R, Wachendorff-Neumann U, Hadano H. WO Patent 2011124539, 2011
- 7a Huang A, Wo K, Lee SY. C, Kneitschel N, Chang J, Zhu K, Mello T, Bancroft L, Norman NJ, Zheng S.-L. J. Org. Chem. 2017; 82: 8864
- 7b Wright SW, Arnold EP, Yang X. Tetrahedron Lett. 2018; 59: 402
- 8a Li J.-X, Li L, Zhou M.-D, Wang H. Org. Chem. Front. 2018; 5: 1003
- 8b Xia T, Hu Z, Ji W, Zhang S, Shi H, Liu C, Pang B, Liu G, Liao X. Org. Chem. Front. 2018; 5: 850
- 9 Prieto A, Bouyssi D, Monteiro N. ACS Catal. 2016; 6: 7197
- 10 Lindsay-Scott PJ, Charlesworth NG, Grozavu A. J. Org. Chem. 2017; 82: 11295
- 11 Despotopoulou C, Klier L, Knochel P. Org. Lett. 2009; 11: 3326
- 12 Chytil M, Engel S, Hanania TG, Alexandrov V, Leahy E. WO Patent 2016130790, 2016
- 13 Kohshi U, Keiko T, Teiji K, Noritaka K, Atsuhiko K, Manabu M, Makoto K, Tadashi O, Koki K, Atsushi S. US Patent Appl. 20020019531, 2002
- 14 The regioselectivity during the alkylation and formylation steps was confirmed by 1H NMR NOESY correlations.
- 15 For the synthesis of compound 13, see: Zhang D, Zhang X, Ai J, Zhai Y, Liang Z, Wang Y, Chen Y, Li C, Zhao F, Jiang H, Geng M, Luo C, Liu H. Bioorg. Med. Chem. 2013; 21: 6804
- 16 Enders D, Berg T, Raabe G, Runsink J. Liebigs Ann. Recl. 1997; 345
- 17 Enantiomeric excess measurements were conducted by chiral supercritical fluid chromatography with comparison to a racemic standard.
- 18 2-MeTHF was utilized as co-solvent during this transformation due to its stability under acidic conditions, see: Aycock DF. Org. Process Res. Dev. 2007; 11: 156