Firstly, 1 mmol of pyrazinoic acid was dissolved in 5 ml of water by heating. Then 1 mmol of aldehyde derivatives and 1.2 mmol isocyanide were added to the reaction mixture, and stirred at room temperature for 4 to 48 hours. The solid obtained was washed with water and filtered and dried in a desiccator. For purification, recrystallization (methanol and water) or plate chromatography (silica gel with 50% ethyl acetate and 50% n-hexane) was applied.
4.2.10. 2-(cyclohexylamino)-1-(2,4-dinitrophenyl)-2-oxoethyl pyrazine-2-carboxylate(P10)
Yield: 88%, mp: 197–199°C, white solid. IR (KBr disk): (3334.18 (NH amid group)), (3106.15 (CH aromatic)), (2937.88-2856.13 (CH aliphatic)), (1744.38 (C = O ester)), (1681. (C = O amid)), (1538.43 (NO2 symmetric stretch)), (1538.43-1450.11 (C = C aromatic)), (1348.34 (NO2 asymmetric stretch)), (1224.20 (C-O ester)) cm− 1. 1H NMR (499 MHz, DMSO-d6) δ (9.31 (s, 1H) H6’, (9.09–8.69 (m, 3H) H2’,3’,3), (8.57 (d, J = 8.5 Hz, 1H)H5), (8.43 (d, J = 7.5 Hz, 1H) NH), (8.01 (d, J = 8.6 Hz, 1H) H6), (6.92 (s, 1H) CH*), (3.58 (s, 1H) H1”), (1.98–1.41 (m, 7H) H2”,4”,6”), 1.18 (ddd, J = 44.5, 20.2, 9.3 Hz, 3H) H5”,3”). 13C NMR (126 MHz, dmso) δ 164.56, 162.91, 149.08, 148.79, 148.07, 146.54, 145.52, 142.70, 136.69, 131.23, 128.50, 120.75, 71.88, 48.82, 40.31, 40.14, 39.97, 39.81, 39.64, 32.47, 32.44, 25.54, 24.86. Elemental analysis calcd (%) for C19H19N5O7 (429.19):C,53.15; H,4.46; N,16.31;found: C,53.22;H,4.53;N,16.38.
4.2.11. 2-(cyclohexylamino)-1-(2-fluorophenyl)-2-oxoethyl pyrazine-2-carboxylate(P11)
Yield: 55%, mp: 143–145°C, white solid. IR (KBr disk): (3265.97 (NH amid group)), (3100.43 (CH aromatic)), (2930.03-2854.01 (CH aliphatic)), (1718.87 (C = O ester)), (1656.95 (C = O amid)), (1569.89-1510.03 (C = C aromatic)), (1187.89 (C-O)), (C-F (967.65)) cm− 1. 1H NMR (499 MHz, DMSO-d6) δ (9.26 (s, 1H) H6’, 8.87 (d, J = 43.6 Hz, 2H) H3’.2’), (8.28 (d, J = 7.6 Hz, 1H) NH), (7.68–7.40 (m, 1H) H5), (7.36–7.06 (m, 1H) H6), (6.40 (s, 1H) CH*), (3.70–3.44 (m, 1H) H1”), (1.85–1.41 (m, 7H) H2”,4”,6”), (1.19 (ddd, J = 44.5, 22.4, 11.2 Hz, 5H) H5”,3”). 13C NMR (126 MHz, dmso) δ 165.74, 163.18, 161.73, 159.76, 148.90, 146.32, 145.40, 142.94, 131.78, 131.72, 130.12, 125.16, 123.30, 123.19, 116.20, 116.03, 70.68, 48.46, 40.49, 40.32, 40.15, 39.98, 39.82, 39.65, 39.48, 32.54, 32.49, 25.57, 24.98, 24.93. Elemental analysis calcd (%) for C19H20FN3O3 (357.15):C,63.85; H,5.64; N,11.76;found: C,63.90;H,5.69;N,11.81.
4.2.12. 2-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxoethyl pyrazine-2-carboxylate(P12)
Yield: 54%, mp: 143–145°C, white solid. IR (KBr disk): (3265.97 (NH amid group)), (3100.43 (CH aromatic)), (2930.03-2854.01 (CH aliphatic)), (1718.87 (C = O ester)), (1656.95 (C = O amid)), (1569.89-1510.03 (C = C aromatic)), (1187.89 (C-O)), (C-F (967.65)) cm− 1. 1H NMR (499 MHz, DMSO-d6) δ (9.32 (s, 1H)H6’), (9.18 (s, 3H) ) HRing (A,B) overlapping multiple), (9.04–8.70 (m, 3H) H2’,3’,5), (8.30 (dd, J = 19.1, 7.9 Hz, 1H) NH), (7.46 (dq, J = 21.6, 11.4, 9.4 Hz, 2H) H6,4), 7.23 (t, J = 7.6 Hz, 1H) H2), (6.14 (s, 1H) CH*), (1.87–1.41 (m, 5H) H1”,2”,6”), (1.42–0.90 (m, 3H) H5”,3”). 13C NMR (126 MHz, dmso) δ 166.43, 163.10, 161.44, 148.89, 148.13, 146.35, 146.02, 145.45, 145.07, 143.00, 138.62, 138.56, 131.08, 131.01, 123.75, 116.08, 115.92, 114.61, 114.43, 75.94, 48.27, 40.48, 40.31, 40.15, 39.98, 39.81, 39.65, 39.48, 32.62, 32.43, 25.55, 24.87, 24.78.
4.2.13. 2-(cyclohexylamino)-1-(4-fluorophenyl)-2-oxoethyl pyrazine-2-carboxylate(P13)
Yield: 56%, mp: 180–182°C, white solid. IR (KBr disk): (3265.97 (NH amid group)), (3100.43 (CH aromatic)), (2930.03-2854.01 (CH aliphatic)), (1718.87 (C = O ester)), (1656.95 (C = O amid)), (1569.89-1510.03 (C = C aromatic)), (1187.89 (C-O)), (C-F (967.65)) cm− 1. 1H NMR (300 MHz, DMSO-d6) δ (9.29 (s, 1H) H6’, (9.03–8.71 (m, 2H) H2’,3’), (8.39–8.21 (m, 2H) H2), (8.09 (dd, J = 8.4, 5.7 Hz, 1H) NH), (7.64 (dd, J = 7.6, 4.7 Hz, 2H)H6), (7.47–7.12 (m, 3H) H3,5) overlapping multiple), (6.09 (d, J = 22.8 Hz, 1H) CH*), 3.50 (s, 1H) H1”), (2.15–1.38 (m, 4H) H2”,4”,6”), (1.12 (dd, J = 30.1, 19.4 Hz, 3H) H3”,5”). 13C NMR (75 MHz, DMSO) δ 166.67, 166.34, 163.99, 163.88, 162.73, 160.63, 148.41, 145.85, 144.97, 142.61, 132.26, 131.85, 131.81, 129.59, 125.79, 116.10, 115.80, 115.53, 115.24, 75.57, 74.95, 47.75, 40.33, 40.06, 39.78, 39.50, 39.22, 38.94, 38.67, 32.20, 32.00, 25.10, 24.43.
4.2.14. 1-(2-chlorophenyl)-2-(cyclohexylamino)-2-oxoethyl pyrazine-2-carboxylate(P14)
Yield: 48%, mp: 138–139°C, white solid. IR (KBr disk): (3308.64 (NH amid group)), (3061.78-3029.67 (CH aromatic)), (2938.15-2850.61(CH aliphatic)), (1738.85(C = O ester)), (1649.84(C = O amid)), (1536.92-1449.65 (C = C aromatic)), (1133.88 (C-O)), (755.87 (C-Cl)) cm− 1. 1H NMR (499 MHz, DMSO-d6) δ (8.33 (d, J = 7.7 Hz, 1H) H6’), (7.86 (d, J = 8.0 Hz, 2H)H3’,2’), (7.71–7.23 (m, 6H) H3,4,5,6,NH overlapping multiple), (6.40 (s, 1H) CH*), (5.24 (s, 1H)H1”), (1.66 (ddd, J = 74.7, 41.4, 13.2 Hz, 6H)H2”,4”,6”), (1.20 (dq, J = 54.4, 14.5, 12.0 Hz, 3H).H5”,3”). 13C NMR (126 MHz, dmso) δ 165.77, 164.27, 134.21, 134.13, 133.69, 131.93, 131.43, 131.22, 130.14, 130.03, 129.45, 128.01, 127.93, 73.40, 48.47, 40.49, 40.32, 40.15, 39.99, 39.82, 39.65, 39.49, 32.51, 25.58, 24.91.
4.2.15. 1-(3-chlorophenyl)-2-(cyclohexylamino)-2-oxoethyl pyrazine-2-carboxylate(P15)
Yield: 49%, mp: 139–141°C, white solid. IR (KBr disk): (3308.64 (NH amid group)), (3061.78-3029.67 (CH aromatic)), (2938.15-2850.61(CH aliphatic)), (1738.85(C = O ester)), (1649.84(C = O amid)), (1536.92-1449.65 (C = C aromatic)), (1133.88 (C-O)), (755.87 (C-Cl)) cm− 1. 1H NMR (300 MHz, DMSO-d6) δ (9.31 (d, J = 1.3 Hz, 1H) H6’), (9.04–8.77 (m, 2H) H3’.2’), (8.36 (d, J = 7.8 Hz, 1H)NH), (7.78–7.32 (m, 4H) H2,4,5,6 overlapping multiple), (6.13 (s, 1H) CH*, (3.66–3.44 (m, 1H) H1”), (1.84–1.35 (m, 6H) H2”,4”,6”), (1.15 (ddd, J = 43.8, 19.5, 9.6 Hz, 4H) H5”,3”). 13C NMR (75 MHz, DMSO) δ 165.96, 162.66, 148.47, 145.89, 144.99, 142.51, 137.83, 133.05, 130.49, 128.69, 127.15, 127.04, 125.92, 75.46, 47.81, 40.33, 40.06, 39.78, 39.50, 39.22, 38.94, 38.67, 32.16, 25.10, 24.41.
4.2.16. 1-(4-chlorophenyl)-2-(cyclohexylamino)-2-oxoethyl pyrazine-2-carboxylate(P16)
Yield: 49%, mp: 139–141°C, white solid. IR (KBr disk): (3308.64 (NH amid group)), (3061.78-3029.67 (CH aromatic)), (2938.15-2850.61(CH aliphatic)), (1738.85(C = O ester)), (1649.84(C = O amid)), (1536.92-1449.65 (C = C aromatic)), (1133.88 (C-O)), (755.87 (C-Cl)) cm− 1. 1H NMR (300 MHz, DMSO-d6) δ (9.30 (s, 1H) H6’), (8.88 (d, J = 20.6 Hz, 2H) H3’,2’), (8.33 (d, J = 7.6 Hz, 1H) NH), (7.80–7.30 (m, 4H) H2,3,5.6 overlapping multiple), (6.13 (s, 1H) CH*), (3.50 (s, 1H) H1”), (1.93–1.44 (m, 7H) H2”,4”,6”), (1.43–0.87 (m, 3H) H5”,3”). 13C NMR (75 MHz, DMSO) δ 166.10, 162.66, 148.41, 145.85, 144.97, 142.54, 134.50, 133.40, 129.18, 128.53, 75.49, 47.76, 40.32, 40.04, 39.76, 39.48, 39.20, 38.93, 38.65, 32.17, 31.97, 25.09, 24.39. Elemental analysis calcd (%) for C19H20ClN3O3 (373.12):C,61.04; H,5.39; N,11.24;found: C,61.12;H,5.47;N,11.32.
4.2.17. 2-(cyclohexylamino)-1-(2,4-dichlorophenyl)-2-oxoethyl pyrazine-2-carboxylate(P17)
Yield: 77%, mp: 164–166°C, white solid. IR (KBr disk): (3325.35 (NH amid group)), (3061.78-3029.67 (CH aromatic)), (2938.15-2850.61(CH aliphatic)), (1738.85(C = O ester)), (1649.84(C = O amid)), (1536.92-1449.65 (C = C aromatic)), (1133.88 (C-O)), (755.87 (C-Cl)) cm− 1. 1H NMR (499 MHz, DMSO-d6) δ (9.26 (s, 1H) H6’), (9.03–8.78 (m, 2H) H3’,2’), (8.36 (d, J = 7.7 Hz, 1H) NH), (7.72 (s, 1H) H3), (7.53 (q, J = 8.7 Hz, 2H) H6,5), (6.44 (s, 1H) CH*), 3.61 (s, 1H) H1”), (1.94–1.41 (m, 6H) H2”,4”,6”), (1.37–0.92 (m, 4H) H5”,3”). 13C NMR (126 MHz, dmso) δ 165.31, 163.10, 149.00, 146.35, 145.47, 142.77, 135.12, 135.05, 132.86, 131.48, 129.66, 128.29, 73.08, 48.56, 40.49, 40.32, 40.16, 39.99, 39.82, 39.65, 39.49, 32.50, 32.48, 25.57, 24.95, 24.91. Elemental analysis calcd (%) for C19H19Cl2N3O3 (407.08):C,55.89; H,4.69; N,10.29;found: C,57.01;H,5.76;N,11.41.
4.2.18. 2-(cyclohexylamino)-2-oxo-1-(p-tolyl)ethyl pyrazine-2-carboxylate(p18)
Yield: 48%, mp: 180–182°C, white solid. IR (KBr disk): (3275.50 (NH amid group)), (3068.59-3037.58 (CH aromatic)), (2939.29-2855.41 (CH aliphatic)), (1731.89 (C = O ester)), (1656.44 (C = O amid)), (1545.71-1494.55 (C = C aromatic)), (1127.78 (C-O)) cm− 1. 1H NMR (499 MHz, DMSO-d6) δ (9.28 (s, 1H) H6’), (8.88 (d, J = 35.5 Hz, 2H) H2’.3’), (8.22 (d, J = 7.6 Hz, 1H) NH), (7.34 (dd, J = 125.5, 7.3 Hz, 4H) H6,5,2,3), (6.08 (s, 1H) CH*), (3.51 (s, 1H) H1”, 2.49 (s, 3H) Me group), (1.85–1.33 (m, 6H) H2”,4”,6”), (1.33–0.83 (m, 4H) H5”,3”). 13C NMR (126 MHz, dmso) δ 166.96, 163.25, 148.79, 146.24, 145.42, 143.18, 138.55, 133.05, 129.46, 127.85, 76.68, 48.20, 40.33, 40.16, 39.99, 39.83, 39.66, 39.49, 32.69, 32.50, 25.59, 24.93, 24.85, 21.24. Elemental analysis calcd (%) for C20H23N3O3 (353.17):C,67.97; H,6.56; N,11.89;found: C,68;H,6.59;N,11.92.
4.2.19. 2-(cyclohexylamino)-2-oxo-1-phenylethyl pyrazine-2-carboxylate(P19)
Yield: 62%, mp: 172–174°C, white solid. IR (KBr disk): (3315.29 (NH amid group)), (3071.59-3030.32 (CH aromatic)), (2933.82-2857.39 (CH aliphatic)), (1725.84 (C = O ester)), (1665.11(C = O amid)), (1549.11-1498.04 (C = C aromatic)), (1131.69 (C-O)) cm− 1.1H NMR (300 MHz, DMSO-d6) δ (9.29 (s, 1H) H6’), (9.05–8.70 (m, 2H) H3’,2)’, (8.29 (d, J = 7.8 Hz, 1H)NH), (7.80–7.24 (m, 5H) H2,3,4,5,6), (6.09 (d, J = 18.1 Hz, 1H) CH*), (3.50 (s, 1H) H1”, (1.88–1.35 (m,6H) H2”,4”,6”), (1.41–0.84 (m,4 H) H3”,5”). 13C NMR (75 MHz, DMSO) δ 166.78, 166.38, 162.77, 148.37, 145.82, 144.96, 142.64, 135.51, 128.67, 128.46, 127.37, 76.24, 47.73, 40.32, 40.04, 39.76, 39.48, 39.20, 38.93, 38.65, 32.21, 32.01, 25.09, 24.43.. Elemental analysis calcd (%) for C19H21N3O3 (339.16):C,67.24; H,6.24; N,12.38;found: C,67.28;H,6.28;N,12.42.
4.2.20. 1-(3-bromophenyl)-2-(cyclohexylamino)-2-oxoethyl pyrazine-2-carboxylate(P20)
Yield: 68%, mp: 142–145°C, white solid. IR (KBr disk): (3224.06 (NH amid group)), (3080.35-3025.97 (CH aromatic)), (2933.07-2854.21(CH aliphatic)), (1739.68(C = O ester)), (1650.87(C = O amid)), (1571.77-1413.39 (C = C aromatic)), (1164.44 (C-O)), (754.90 (C-Br)) cm− 1. 1H NMR (300 MHz, DMSO-d6) δ (9.30 (s, 1H) H6’), (8.89 (d, J = 20.3 Hz, 2H) H2’,3’), (8.36 (d, J = 7.4 Hz, 1H) NH), (8.01–7.17 (m, 4H) H2,4,5,6), (6.09 (d, J = 18.5 Hz, 1H) CH*), (3.50 (s, 1H) H1”), (1.91–1.41 (m, 6H) H2”,4”,6”), (1.39–0.80 (m, 4H) H5”,3”). 13C NMR (75 MHz, DMSO) δ 165.94, 162.64, 148.44, 145.87, 144.97, 142.49, 138.03, 131.58, 130.75, 130.03, 129.90, 126.34, 121.56, 75.39, 47.79, 40.32, 40.04, 39.76, 39.48, 39.21, 38.93, 38.65, 31.97, 25.07, 24.39. Elemental analysis calcd (%) for C19H21BrN3O3 (417.07):C,54.56; H,4.82; N,10.05; found: C,54.49; H,4.75; N,9.98.