Gemini 200

1,25-Dihydroxyvitamin D₂ and the analogs PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734 (Figure 9) were synthesized [62 (link)] at the Chemistry Department of the Pharmaceutical Research Institute, Warsaw, Poland. The compounds gave analytical data (¹H and ¹³C NMR spectra, recorded on a Varian GEMINI-200, Varian S 500 and Varian S 600 spectrometers, Varian Medical Systems, Inc., Palo Alto, CA, USA; UV spectra, taken in ethanolic solutions on a Shimadzu UV-160A spectrophotometer, Shimadzu Corp., Kyoto, Japan; mass spectra (MS) and high-resolution MS (HRMS), recorded on a Maldi Spectrometer SYNAPT G2-S HDMS; Waters Corp., Milford, MA, USA) consistent with the assigned structures. Amber glass ampoules were filled with ethanolic solution of 50 μg of analogs and the solutions were dried down under a stream of argon and the ampoules flame sealed. The quantity of an analog in an ampoule was confirmed by UV.

Nuclear magnetic resonance spectroscopy (NMR) is a widely used structure-determining method today. ¹H-NMR and ¹³C-NMR analyses were performed on a Gemini-200 device (Varian) at room temperature. For the determination of the proton spectra, 20–40 mg of sample was diluted in approx. 0.6 mL of denatured chloroform and for the carbon spectra, 40 mg of the sample was diluted in the same way. The spectra were evaluated using a program called ACV SpecView.

Chemicals, solvents and reagents (R-phenylpiperazines) used for the syntheses were purchased from Sigma-Aldrich (Milan, Italy), and were used without any further purification. Melting points (uncorrected) were determined with a Büchi apparatus (Milan, Italy). ¹H NMR spectra and ¹³C NMR spectra were recorded on a Varian Gemini-200 instrument at 200 and 50 MHz, respectively; DMSO-d₆; δ in ppm rel. to Me₄Si as internal standard. J in Hz. Elemental analyses were performed on a Flash 2000 CHNS (Thermo Scientific, Milan Italy) instrument in the Microanalysis Laboratory of the Department of Pharmacy, University of Genova. The results of elemental analyses indicated that the purity of all compounds was ≥95%.

The following instruments and parameters were used: melting points: Boethius HMK apparatus (Veb Analytic, Dresden, Germany); IR spectra: KBr pellets, 400–4000 cm⁻¹ Thermo Mattson Satellite FTIR spectrophotometer (Thermo Mattson, Madison, WI, USA); ¹H- and ¹³C-NMR spectra: Gemini 200 at 200 and 50 MHz (¹³C), respectively, or Unity 500 Plus apparatus at 500 MHz and 125 MHz (¹³C) (Varian, Palo Alto, CA, USA); chemical shifts are expressed at δ in ppm values relative to TMS as standard. LC-MS analyses of compound 37 was performed on a: LCMS-ESI-IT-TOF LC-20A mass spectrometer (Shimadzu Scientific Instruments, Columbia, MD, USA) in positive ion mode. Elemental analyses (C,H,N) were performed on 2400 Series II CHN Elemental Analyzer (Perkin Elmer, Shelton, CT, USA). Thin-layer chromatography was performed on silica gel 60 F254 TLC plates (Merck, Darmstadt, Germany) using benzene/ethanol (4:1) as mobile phases, and visualized with UV light 254 or 366 nm.
Marvin ver. 17.9, was used for drawing, displaying and characterizing chemical structures, substructures and reactions (ChemAxon, http://www.chemaxon.com, 2017).
The starting 4-chloro-3-pyridinesulfonamide (1) was commercially available (Alfa Aesar, Karlsruhe, Germany), and primary 4-substituted pyridine-3-sulfonamides 2–14 were obtained according to previously described methods (2–11 [15 (link)] and 12–14 [13 (link)]).

N,N,N,N-tetramethyl-1,3-propanediamine (0.01 mol) was dissolved in acetonitrile. Benzyl chloride (0.02 mol) was then added after that the mixture was refluxed at 80 °C for 2 h. Product crystallization was performed 3 times using ethanol with a yield of 80% at a melting point of 70 °C. Figure 1 shows a summary of the preparation process. The structure of the synthesized compound was confirmed using FT-IR spectroscopic analysis with KBr pellets on Perkin Elmer in Egyptian Petroleum Research Institute. ¹H-NMR spectroscopy was carried out in dimethyl sulfoxide (DMSO) using a Varian Gemini-200 MHz system.Figure 1

Preparation of the ionic liquid.