ACS Combinatorial Science
Research Article
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performed using Kieselgel Merck 60 (230−400 mesh) as the
stationary phase. Melting points were determined on a Buchi
melting point apparatus and are uncorrected. IR spectra were
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1
recorded on Perkin-Elmer Spectrum BX II. H and 13C NMR
spectra were acquired on Bruker Avance DRX 500
spectrometer using DMSO-d6 as a solvent. The spectra were
referenced to the peak of DMSO-d5. LC-MS data were
recorded on Agilent 1100 HPLC equipped with diode-matrix
and mass-selective detector Agilent LC-MSD SL, Column,
Zorbax SB-C18, 4.6 mm ×15 mm. Eluent, A, acetonitrile−water
with 0.1% of TFA (95:5, v/v); B, water with 0.1% of TFA. Flow
rate: 1.8 mL/min. Ionization method: Atmospheric Pressure
Chemical Ionization (APCI). The purification of the
compounds was performed using a Companion Combi-Flash
instrument with UV-detector and a reusable LukNova column
[eluent, A, CHCl3; B, CHCl3:methanol (7:3, v/v)]. According
to HPLC-MS data the synthesized sulfonamides have purity
over 95%.
General Procedure for Parallel Synthesis of Aliphatic
Sulfonamides. Alkyl sulfonyl halide 1 (1 mmol) was added to
a solution of an alkyl amine 2 (1 mmol) and triethylamine (1.1
mmol) in acetonitrile (0.6 mL). The obtained mixture was left
staying in a sealed vial at the bench at room temperature
overnight. To achieve full conversion, the mixture was then
sonicated at 80 °C for 2 or 4 h in experiments with sulfonyl
chlorides or the fluorides, respectively (Figure S1, in the
Supporting Information). Then, the mixture was cooled down
to room temperature, diluted with chloroform (3 mL) and
washed with water (3 × 7 mL). The organic phase was
separated and the solvent was removed in vacuum. The crude
product with purity below 95% was purified by flash
chromatography.
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ASSOCIATED CONTENT
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S
* Supporting Information
(16) Bebernitz, G. R.; Aicher, T. D.; Stanton, J. L.; Gao, J.; Shetty, S.
S.; Knorr, D. C.; Strohschein, R. J.; Tan, J.; Brand, L. J.; Liu, C.; et al.
Anilides of (R)-Trifluoro-2-Hydroxy-2-Methylpropionic Acid as
Inhibitors of Pyruvate Dehydrogenase Kinase. J. Med. Chem. 2000,
43, 2248−2257.
Details of experimental synthetic procedures; analytical and
spectroscopic data for selected synthesized compounds. This
material is available free of charge via the Internet at http://
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in Organic Synthesis. I. The Synthesis of Aminobenzenesulfonyl
Fluorides and Their Condensation with β-Ketonic Esters. J. Org. Chem.
1963, 28, 3426−3430.
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Synthesis of β-Aminoethanesulfonyl Fluorides or 2-Substituted
Taurine Sulfonyl Fluorides as Potential Protease Inhibitors. Tetrahe-
dron Lett. 2009, 3391−3393.
(19) Brouwer, A. J.; Ceylan, T.; Jonker, A. M.; van der Linden, T.;
Liskamp, R. M. J. Synthesis and Biological Evaluation of Novel
Irreversible Serine Protease Inhibitors Using Amino Acid Based
Sulfonyl Fluorides as an Electrophilic Trap. Bioorg. Med. Chem. 2011,
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Sulfur Center. 22. Nucleophilic Substitution Reaction of Phenyl-
methanesulfonyl Halides with Anilines. J. Am. Chem. Soc. 1987, 109,
7472−7477.
AUTHOR INFORMATION
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Corresponding Authors
Notes
The authors declare no competing financial interest.
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