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was checked by TLC (Silufol UV 254, Kavalier Votice, Czech Republic) using petroleum ether/EtOAc
(9:1) as developing solvents. The plates were visualized using UV light (254 nm). Melting points
(uncorrected) were determined on Boetius PHMK 05 (VEB Kombinat Nagema, Radebeul, Germany).
Elemental analyses were performed on the automatic microanalyser CHNS-O CE instrument (FISONS
EA 1110, Milano, Italy). Infrared spectra were recorded in Nicolet Impact 400 spectrometer in KBr
pellets. 1H- and 13C-NMR spectra were recorded on a Varian Mercury – Vx BB 300 (Varian, Palo Alto
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CA, USA), operating at 299.95 MHz for H- and 75.43 MHz for C-, in CDCl3 solutions at ambient
temperature. The chemical shifts δ are given in ppm related to tetramethylsilane (TMS) as an internal
standard. The coupling constants (J) are reported in Hz.
General procedure for pyrazinecarboxamide synthesis.
A mixture of acid, i.e. pyrazine-2-carboxylic, 6-chloropyrazine-2-carboxylic [15], 5-tert-
butylpyrazine-2-carboxylic [16] or 5-tert-butyl-6-chloropyrazine-2-carboxylic [5] acids, respectively,
(50.0 mmol) and thionyl chloride (5.5 mL, 75.0 mmol) in dry toluene (20 mL) was refluxed for about 1
h. Excess of thionyl chloride was removed by repeated evaporation with dry toluene in vacuo. The
crude acyl chloride dissolved in dry acetone (50 mL) was added dropwise to a stirred solution of the
corresponding substituted amine (50.0 mmol) in 50 mL of dry pyridine at room temperature. After the
addition was complete, stirring continued for another 30 min. The reaction mixture was then poured
into 100 mL of cold water and the crude amide was collected and recrystallised from aqueous ethanol.
6-Chloro-N-(4-chloro-3-methylphenyl)-pyrazine-2-carboxamide (1). Yield 47%; Anal. Calcd. for
C12H9Cl2N3O (282.1): 51.09% C, 3.22% H, 14.89% N; Found: 50.81% C, 3.11% H, 14.64% N; Mp
137 °C; Log P: 2.53; Clog P: 3.43369; TLC: RF = 0.82; IR cm-1: 3343 (N-H), 2926 (methyl), 1690
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(C=O), 1589 (phenyl), 1541 (N-H), 1377, 1172, 1144, and 1009 (pyrazine); H-NMR δ: 9.38 (1H, s,
H3), 9.34 (1H, bs, NH), 8.81 (1H, s, H5), 7.66 (1H, d, J=2.6 Hz, H2´), 7.54 (1H, dd, J=8.5 Hz, J=2.6
Hz, H6´), 7.34 (1H, d, J=8.5 Hz, H5´), and 2.40 (3H, s, CH3); 13C-NMR δ: 159.3, 147.6, 147.4, 143.8,
142.2, 137.0, 135.3, 130.4, 129.6, 122.2, 118.7, and 20.2.
6-Chloro-N-(3-iodo-4-methylphenyl)-pyrazine-2-carboxamide (2). Yield 83%; Anal. Calcd. for
C12H9ClIN3O (373.6): 38.58% C, 2.43% H, 11.25% N; Found: 38.80% C, 2.62% H, 11.37% N. Mp
173.4-174.5 °C; Log P: 3.33; Clog P: 3.54369; TLC: RF = 0.81. IR cm-1: 3321 (N-H), 2975 (methyl),
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1667 (C=O), 1598 (phenyl), 1530 (N-H), 1371, 1300, 1167, 1118, and 1012 (pyrazine); H-NMR δ:
9.38 (1H, s, H3), 9.32 (1H, bs, NH), 8.81 (1H, s, H5), 8.21 (1H, d, J=2.2 Hz, H2´), 7.68 (1H, dd, J=8.2
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Hz, J=2.2 Hz, H6´), and 7.24 (1H, d, J=8.2 Hz, H5´), 2.42 (3H, s, CH3); C-NMR δ: 159.2, 147.6,
147.4, 143.7, 142.2, 138.3, 135.3, 129.9, 129.7, 119.8, 100.8, and 27.5
5-tert-Butyl-N-(4-chloro-3-methylphenyl)-pyrazine-2-carboxamide (3). Yield 86%; Anal. Calcd. for
C16H18ClN3O (303.8): 63.26% C, 5.97% H, 13.83% N; Found: 63.44% C, 6.11% H, 13.54% N; Mp
122 °C; Log P: 3.76; Clog P: 4.53404; TLC: RF = 0.94; IR cm-1: 3425 (N-H), 2965, 2933, 2921, 2869
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(tert-butyl, methyl), 1688 (C=O), 1587 (phenyl), 1519 (N-H), 1407, 1278, and 1143 (pyrazine); H-
NMR δ: 9.60 (1H, bs, NH), 9.38 (1H, d, J=1.5 Hz, H3), 8.61 (1H, d, J=1.5 Hz, H6), 7.69 (1H, d, J=2.5
Hz, H2´), 7.52 (1H, dd, J=8.5 Hz, J=2.5 Hz, H6´), 7.32 (1H, d, J=8.5 Hz, H5´), 2.39 (3H, s, CH3), and