3.2. Synthesis
3.2.1. General Procedure for the Synthesis of the β-Keto Esters (2a–2e)
A 10% aqueous solution of KOH (5.6 mL) was added dropwise under stirring to form a suspension of compound 1 (10 mmol) in DMF (10 mL). Then, ethyl 2-chloroacetoacetate (1.4 mL, 10 mmol) was added and the mixture was stirred at 25 °C for 30 min. Then, the mixture was poured into ice water to obtain compound 2, which was filtered and washed with water, and then subsequently recrystallized from ethyl acetate.
Ethyl 2-((6-(2-chlorobenzyl)-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio)-3-oxobutanoate (2a): White solid; Yield: 73.12%; mp: 129.4–130.1 °C; IR (KBr): υ 3260, 2986, 2950, 1743, 1653, 1575, 1482, 1422, 1309, 1184, 1018, 750, 686 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 7.79 (s, 1H), 7.46 (dt, J = 7.6, 2.9 Hz, 1H), 7.39–7.24 (m, 3H), 5.16 (s, 1H), 4.21 (qd, J = 7.1, 3.0 Hz, 2H), 4.09–3.94 (m, 2H), 1.79 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H); HRMS (m/z): calcd. for C16H17ClN3O4S (M + H+) 382.06283, found 382.06076.
Ethyl 2-((6-(4-chlorobenzyl)-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio)-3-oxobutanoate (2b): White solid; Yield: 75.34%; mp: 126.8–128.7 °C; IR (KBr): υ 3392, 3100, 2982, 2933, 1721, 1654, 1580, 1501, 1407, 1316, 1273, 1203, 806 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 7.85 (s, 1H), 7.42–7.32 (m, 2H), 7.33–7.17 (m, 2H), 5.15 (s, 1H), 4.22 (tdd, J = 7.2, 5.5, 2.5 Hz, 2H), 3.93–3.75 (m, 2H), 1.89 (s, 3H), 1.26 (d, J = 7.1 Hz, 3H); HRMS (m/z): calcd. for C16H17ClN3O4S (M + H+) 382.06283, found 382.06247.
Ethyl 2-((6-(4-fluorobenzyl)-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio)-3-oxobutanoate (2c): White solid; Yield: 72.69%; mp: 125.1–125.4 °C; IR (KBr): υ 3388, 2987, 2930, 1724, 1659, 1578, 1505, 1410, 1316, 1210, 1021, 810 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 7.88 (d, J = 33.9 Hz, 1H), 7.36–7.25 (m, 2H), 7.18–7.09 (m, 2H), 5.15 (s, 1H), 4.22 (qd, J = 7.1, 2.0 Hz, 2H), 3.94–3.79 (m, 2H), 1.89 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H); HRMS (m/z): calcd. for C16H17FN3O4S (M + H+) 366.09238, found 366.09278.
Ethyl 3-oxo-2-((5-oxo-6-(4-(trifluoromethyl)benzyl)-2,5-dihydro-1,2,4-triazin-3-yl)thio)butanoate (2d): White solid; Yield: 76.52%; mp: 128.1–128.7 °C; IR (KBr): υ 3121, 2997, 1741, 1633, 1580, 1501, 1434, 1368, 1263, 1170, 1028, 856 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 7.84 (s, 1H), 7.44–7.36 (m, 2H), 7.31 (d, J = 8.2 Hz, 2H), 5.15 (s, 1H), 4.22 (qd, J = 7.1, 2.1 Hz, 2H), 3.99–3.84 (m, 2H), 1.89 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H); HRMS (m/z): calcd. for C17H20F3N4O4S (M + NH4+) 433.11574, found 433.08624.
Ethyl 2-((6-(4-methoxybenzyl)-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio)-3-oxobutanoate (2e): Yellow solid; Yield: 80.38%; mp: 131.2–132.6 °C; IR (KBr): υ 3215, 2986, 2947, 1731, 1630, 1573, 1494, 1424, 1304, 1247, 1179, 1095, 820 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 7.85 (s, 1H), 7.24–7.15 (m, 2H), 6.90–6.81 (m, 2H), 5.15 (s, 1H), 4.22 (qd, J = 7.1, 2.0 Hz, 2H), 3.87–3.73 (m, 2H), 3.72 (s, 3H), 1.91 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H); HRMS (m/z): calcd. for C17H20N3O5S (M + H+) 378.11237, found 378.10079.
3.2.2. General Procedure for the Synthesis of Ethyl 6-Aryl-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylates (3a–3e)
Compound 2 (0.01 mol) was added to PPA (85% P2O5) (10.0 g). The mixture was irradiated in a microwave at 120 °C for 20 min at a power of 400 W. The reaction mixture was then poured into ice water. The resulting solid was filtered, washed with cold water (3 × 20 mL) and dried. The crude product was recrystallized from ethyl acetate to give compound 3.
Ethyl 6-(2-chlorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylate (3a): White solid; Yield: 81.24%; mp: 162.3–163.3 °C; IR (KBr): υ 3059, 2986, 2941, 1697, 1609, 1495, 1474, 1242, 1196, 760 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.41 (ddd, J = 8.7, 5.4, 3.5 Hz, 2H), 7.26 (dd, J = 5.8, 3.5 Hz, 2H), 4.40 (q, J = 7.1 Hz, 2H), 4.33 (s, 2H), 2.60 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 163.94, 160.49, 158.92, 154.33, 143.13, 134.72, 133.15, 131.81, 129.45, 128.65, 126.85, 109.99, 62.43, 35.14, 14.17, 11.86; HRMS (m/z): calcd. for C16H15ClN3O3S (M + H+) 364.05226, found 364.05240.
Ethyl 6-(4-chlorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylate (3b): White solid; Yield: 85.12%; mp: 130.7–132.1 °C; IR (KBr): υ 3030, 2984, 2960, 1715, 1585, 1501, 1463, 1285, 1221, 808 cm−1; 1H-NMR (600 MHz, DMSO-d6) δ 7.35 (s, 4H), 4.33 (q, J = 7.1 Hz, 2H), 4.01 (s, 2H), 2.61 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 164.05, 160.45, 158.82, 155.18, 142.98, 133.54, 133.04, 130.93, 128.66, 110.28, 62.50, 36.61, 14.18, 12.08; HRMS (m/z): calcd. for C16H15ClN3O3S (M + H+) 364.05226, found 364.05270.
Ethyl 6-(4-fluorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylate (3c): White solid; Yield: 83.78%; mp: 128.3–129.1 °C; IR (KBr): υ 3066, 2984,2938, 1715,1501,1463, 1285, 1221, 808 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.39 (dd, J = 8.6, 5.4 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 4.42 (q, J = 7.1 Hz, 2H), 4.13 (s, 2H), 2.76 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 164.03, 163.21, 160.77, 160.48, 158.84, 155.42, 142.99, 131.18, 131.10, 115.49, 115.28, 110.20, 62.48, 36.46, 14.17, 12.06; HRMS (m/z): calcd. for C16H15FN3O3S (M + H+) 348.08182, found 348.08240.
Ethyl 3-methyl-7-oxo-6-(4-(trifluoromethyl)benzyl)-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylate (3d): White solid; Yield: 80.12%; mp: 94.9–95.2 °C; IR (KBr): υ 2998, 2918, 1720, 1490, 1267, 1161, 816 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.45 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 4.42 (q, J = 7.1 Hz, 2H), 4.16 (s, 2H), 2.77 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 165.36, 158.74, 156.67, 156.37, 154.83, 152.49, 148.11, 146.62, 130.59, 120.73, 109.93, 62.23, 36.25, 13.85, 11.79; HRMS (m/z): calcd. for C17H18F3N4O3S (M + NH4+) 415.10517, found 415.07679.
Ethyl 6-(4-methoxybenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylate (3e): Yellow solid; Yield: 87.66%; mp: 105.3–105.5 °C; IR (KBr): υ 2982, 2918, 1721, 1695, 1659, 1613, 1575, 1505, 1368, 1290, 1242, 1174, 1131, 1052, 1028, 815 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.38–7.30 (m, 2H), 6.91–6.82 (m, 2H), 4.41 (q, J = 7.1 Hz, 2H), 4.10 (s, 2H), 3.81 (s, 3H), 2.77 (s, 3H), 1.42 (d, J = 7.1 Hz, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 163.95, 160.54, 158.94, 158.67, 155.75, 143.08, 130.61, 127.04, 113.94, 109.98, 62.43, 55.24, 36.35, 14.18, 12.09; HRMS (m/z): calcd. for C17H18N3O4S (M + H+) 360.10180, found 360.09732.
3.2.3. General Procedure for the Synthesis of 6-Aryl-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acids (4a–4e)
The ester derivative (3) (4.0 mmol) was hydrolyzed by treatment with a mixture of NaOH 10% (10 mL) and CH3OH (10 mL) for 2 h at 25 °C. The solution was concentrated to half volume and the product was precipitated by acidification with 10% HCl to pH value of 3.0, filtered, washed with water, then dried.
6-(2-Chlorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid (4a): White solid; Yield: 95.35%; mp: 209.6–210.4 °C; IR (KBr): υ 2920, 1629,1577, 1475, 1440, 1351, 1038, 751 cm−1; 1H-NMR (600 MHz, DMSO-d6) δ 7.46 (dd, J = 7.5, 1.8 Hz, 1H), 7.42–7.37 (m, 1H), 7.31–7.26 (m, 2H), 4.13 (s, 2H), 2.46 (s, 3H); 13C-NMR (101 MHz, DMSO-d6) δ 164.01, 162.63, 158.99, 153.55, 134.20, 133.96, 131.91, 129.55, 129.11, 127.48, 34.79, 11.68; HRMS (m/z): calcd. for C14H11ClN3O3S (M + H+) 336.02096, found 336.02300.
6-(4-Chlorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid (4b): White solid; Yield: 93.11%; mp: 197.2–198.2 °C; IR (KBr): υ 2959, 2927, 1717, 1649, 1613, 1575, 1484, 1417, 1356, 1242, 1093, 803 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 7.37 (s, 4H), 4.02 (s, 2H), 2.61 (s, 3H); 13C-NMR (101 MHz, DMSO-d6) δ 164.10, 162.66, 159.00, 154.26, 142.19, 135.29, 131.78, 131.61, 131.10, 128.60, 36.51, 12.04; HRMS (m/z): calcd. for C14H11ClN3O3S (M + H+) 336.02096, found 336.02190.
6-(4-Fluorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid (4c): White solid; Yield: 91.34%; mp: 205.9–206.2 °C; IR (KBr): υ 2950, 1697, 1569, 1507, 1470, 1287, 1252, 1015, 809 cm−1; 1H-NMR (600 MHz, DMSO-d6) δ 7.36 (dd, J = 8.4, 5.5 Hz, 2H), 7.12 (t, J = 8.8 Hz, 2H), 3.99 (s, 2H), 2.59 (s, 3H); 13C-NMR (101 MHz, DMSO-d6) δ 164.10, 162.76, 162.61, 160.35, 159.02, 154.49, 132.33, 132.30, 131.67, 131.59, 115.52, 115.30, 36.34, 12.07; HRMS (m/z): calcd. for C14H11FN3O3S (M + H+) 320.05052, found 320.05222.
3-Methyl-7-oxo-6-(4-(trifluoromethyl)benzyl)-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid (4d): White solid; Yield: 89.88%; mp: 212.6–213.8 °C; IR (KBr): υ 3049, 2957, 1711, 1612, 1508, 1476, 1423, 1381, 1354, 1286, 921, 779, 764 cm−1; 1H-NMR (600 MHz, DMSO-d6) δ 7.46 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 4.04 (s, 2H), 2.59 (s, 3H); 13C-NMR (101 MHz, DMSO-d6) δ 164.15, 162.64, 159.01, 154.23, 147.57, 142.45, 135.81, 131.59, 121.77, 121.32, 119.23, 36.50, 12.05; HRMS (m/z): calcd. for C15H11F3N3O3S (M + NH4+) 387.07387, found 387.04752.
6-(4-Methoxybenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid (4e): Yellow solid; Yield: 94.50%; mp: 209.8–210.8 °C; IR (KBr): υ 2944, 2835, 2752, 2595, 2503, 1709, 1662, 1618, 1580, 1486, 1434, 1359, 1273, 1244, 1184, 1026, 767 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 14.27 (s, 1H), 7.30–7.21 (m, 2H), 6.91–6.82 (m, 2H), 3.94 (s, 2H), 3.72 (s, 3H), 2.63 (s, 3H); 13C-NMR (101 MHz, DMSO-d6) δ 164.05, 162.64, 158.98, 158.49, 154.80, 142.91, 130.77, 127.88, 114.12, 110.63, 55.44, 36.29, 12.17; HRMS (m/z): calcd. for C15H14N3O4S (M + H+) 332.07050, found 332.07303.
3.2.4. General Procedure for the Synthesis of the Target Compounds 5a–5j
Substituted primary amine (1.0 mmol) was added to a solution of compound 4 (1.0 mmol), HOBt (1-hydroxybenzotriazole, 0.15 g, 1.1 mmol), triethylamine (0.34 g, 3.3 mmol), and EDCl (N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, 0.21 g, 1.1 mmol) in DCM (dichloromethane, 30 mL). The solution was then stirred at 25 °C for 16 h. The reaction was diluted with H2O (30 mL), and the organic layer was separated and sequentially washed with 1 mol·L−1 HCl (10 mL), saturated NaHCO3 aqueous solution (10 mL), and brine (10 mL), dried (Na2SO4). The solvent was filtrated and evaporated, resulting in the crude product which was purified by chromatography (CH2Cl2-CH3OH, V:V = 50:1).
6-(2-Chlorobenzyl)-N-(furan-2-ylmethyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5a): White solid; Yield: 72.60%; mp: 138.5–139.0 °C; IR (KBr): υ 3331, 3055, 2926, 1655, 1609, 1570, 1487, 1443, 1344, 748 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.40 (qd, J = 5.7, 3.5 Hz, 3H), 7.25 (dd, J = 5.8, 3.5 Hz, 2H), 6.41–6.30 (m, 2H), 6.06 (s, 1H), 4.61 (d, J = 5.1 Hz, 2H), 4.32 (s, 2H), 2.56 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 162.97, 159.67, 159.13, 154.08, 150.16, 142.44, 139.14, 134.65, 133.09, 131.74, 129.45, 129.40, 128.66, 126.84, 113.35, 110.53, 108.17, 37.07, 35.12, 12.11; HRMS (m/z): calcd. for C19H16ClN4O3S (M + H+) 415.06316, found 415.06469.
N,6-Bis(2-chlorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5b): White solid; Yield: 72.20%; mp: 148.1–149.4 °C; IR (KBr): υ 3271, 3073, 2940, 1663, 1614, 1575, 1504, 1440, 1352, 752 cm–1; 1H-NMR (400 MHz, Chloroform-d) δ 7.48–7.36 (m, 4H), 7.32–7.20 (m, 4H), 6.35 (s, 1H), 4.69 (d, J = 5.4 Hz, 2H), 4.31 (s, 2H), 2.54 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 163.00, 159.79, 159.04, 154.06, 138.74, 134.66, 134.57, 133.57, 133.11, 131.74, 130.37, 129.62, 129.45, 129.31, 128.66, 127.17, 126.84, 113.68, 42.34, 35.11, 12.11; HRMS (m/z): calcd. for C21H17Cl2N4O2S (M + H+) 459.04493, found 459.06700.
6-(2-Chlorobenzyl)-N-(2,4-dichlorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5c): White solid; Yield: 71.40%; mp: 209.8–252.4 °C; IR (KBr): υ 3254, 3062, 2928, 1638, 1616, 1570, 1541, 1487, 1441, 1387, 756 cm–1; 1H-NMR (400 MHz, Chloroform-d) δ 7.46–7.32 (m, 4H), 7.30–7.20 (m, 3H), 6.48 (d, J = 6.1 Hz, 1H), 4.65 (d, J = 5.9 Hz, 2H), 4.30 (s, 2H), 2.54 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 162.90, 159.75, 158.96, 154.20, 139.15, 134.70, 134.65, 134.30, 133.10, 131.78, 131.50, 129.54, 129.47, 128.68, 127.54, 126.86, 112.96, 41.88, 35.15, 12.10; HRMS (m/z): calcd. for C21H16Cl3N4O2S (M + H+) 493.00595, found 493.0835.
6-(2-Chlorobenzyl)-N-(4-fluorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5d): White solid; Yield: 69.90%; mp: 153.5–154.4 °C; IR (KBr): υ 3059, 2922, 2851, 1640, 1578, 1509, 1480, 1434, 1385, 765 cm–1; 1H-NMR (400 MHz, Chloroform-d) δ 7.42–7.24 (m, 6H), 7.08–7.03 (m, 2H), 6.34 (s, 1H), 4.57 (d, J = 5.6 Hz, 2H), 4.29 (s, 2H), 2.55 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 163.38, 162.90, 160.93, 159.82, 159.18, 154.02, 139.13, 134.61, 133.32, 133.28, 133.03, 131.67, 129.73, 129.65, 129.47, 128.69, 126.85, 115.61, 115.40, 113.53, 43.52, 35.10, 12.13; HRMS (m/z): calcd. for C21H17ClFN4O2S (M + H+) 443.07448, found 443.07726.
6-(2-Chlorobenzyl)-3-methyl-N-(4-methylbenzyl)-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5e): White solid; Yield: 72.00%; mp: 166.6–167.3 °C; IR (KBr): υ 2920, 2851, 1654, 1569, 1532, 1476, 1440, 1384, 764 cm–1; 1H-NMR (400 MHz, Chloroform-d) δ 7.39 (ddd, J = 11.2, 5.5, 3.5 Hz, 2H), 7.30–7.15 (m, 6H), 6.09 (s, 1H), 4.56 (d, J = 5.3 Hz, 2H), 4.30 (s, 2H), 2.55 (s, 3H), 2.36 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 162.85, 159.64, 159.06, 154.07, 139.02, 137.69, 134.68, 134.03, 133.13, 131.76, 129.48, 129.46, 128.66, 127.93, 126.84, 113.25, 44.13, 35.11, 21.10, 12.09; HRMS (m/z): calcd. for C22H20ClN4O2S (M + H+) 439.09955, found 439.10209.
6-(4-Chlorobenzyl)-N-(4-fluorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5f): White solid; Yield: 70.20%; mp: 210.8–211.2 °C; IR (KBr): υ 3246, 3076, 2939, 1652, 1607, 1570, 1532, 1508, 1373, 1352, 836, 807 cm–1; 1H-NMR (400 MHz, Chloroform-d) δ 7.39–7.25 (m, 6H), 7.07 (t, J = 8.6 Hz, 2H), 6.18 (s, 1H), 4.59 (d, J = 5.7 Hz, 2H), 4.10 (s, 2H), 2.72 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 162.83, 159.62, 158.86, 155.06, 139.42, 133.46, 133.10, 130.88, 129.78, 129.70, 128.69, 115.91, 115.69, 112.72, 43.65, 36.61, 12.33; HRMS (m/z): calcd. for C21H17ClFN4O2S (M + H+) 443.07448, found 443.07610.
6-(4-Fluorobenzyl)-N-(furan-2-ylmethyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5g): White solid; Yield: 73.30%; mp: 155.4–155.8 °C; IR (KBr): υ 3231, 3126, 3063, 2932, 1636, 1568, 1508, 1479, 1418, 1346, 812 cm–1; 1H-NMR (400 MHz, Chloroform-d) δ 7.39 (dd, J = 1.8, 0.8 Hz, 1H), 7.38–7.32 (m, 2H), 7.05–6.94 (m, 2H), 6.42–6.28 (m, 3H), 4.61 (d, J = 5.4 Hz, 2H), 4.10 (s, 2H), 2.71 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 163.15, 163.05, 160.71, 159.68, 159.08, 155.09, 150.27, 142.38, 139.06, 131.11, 131.03, 130.72, 130.69, 115.44, 115.22, 113.46, 110.52, 108.15, 37.04, 36.44, 12.31; HRMS (m/z): calcd. for C19H16FN4O3S (M + H+) 399.09271, found 399.09391.
N-(2-Chlorobenzyl)-6-(4-fluorobenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5h): White solid; Yield: 69.40%; mp: 161.7–162.9 °C; IR (KBr): υ 3331, 3057, 2937, 1639, 1616, 1572, 1510, 1477, 1441, 1348, 804, 752 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.50–7.27 (m, 6H), 7.01 (t, J = 8.7 Hz, 2H), 6.27 (s, 1H), 4.71 (d, J = 5.9 Hz, 2H), 4.11 (s, 2H), 2.71 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 163.16, 163.07, 160.71, 159.81, 159.01, 155.07, 138.76, 134.62, 133.52, 131.09, 131.01, 130.72, 130.69, 130.21, 129.59, 129.22, 127.12, 115.45, 115.24, 113.70, 42.28, 36.42, 12.29; HRMS (m/z): calcd. for C21H17ClFN4O2S (M + H+) 443.07448, found 443.07588.
N-(Furan-2-ylmethyl)-6-(4-methoxybenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5i): White solid; Yield: 75.00%; mp: 142.6–143.6 °C; IR (KBr): υ 3215, 2924, 2842, 1646, 1569, 1509, 1475, 1393, 814 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.41 (dd, J = 1.8, 0.8 Hz, 1H), 7.35–7.27 (m, 2H), 6.88–6.80 (m, 2H), 6.41–6.31 (m, 2H), 6.26 (s, 1H), 4.62 (d, J = 5.2 Hz, 2H), 4.07 (s, 2H), 3.80 (s, 3H), 2.72 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 162.95, 159.74, 159.17, 158.65, 155.44, 150.25, 142.42, 139.16, 130.54, 126.98, 113.90, 113.14, 110.53, 108.18, 55.23, 37.05, 36.33, 12.33; HRMS (m/z): calcd. for C20H19N4O4S (M + H+) 411.11270, found 411.11199.
N-(2-chlorobenzyl)-6-(4-methoxybenzyl)-3-methyl-7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxamide (5j): White solid; Yield: 71.50%; mp: 156.4–172.2 °C; IR (KBr): υ 3258, 1656, 1610, 1570, 1512, 1350, 1300, 1036, 752 cm−1; 1H-NMR (400 MHz, Chloroform-d) δ 7.49–7.38 (m, 2H), 7.34–7.24 (m, 4H), 6.88–6.80 (m, 2H), 6.52 (s, 1H), 4.70 (d, J = 5.3 Hz, 2H), 4.06 (s, 2H), 3.79 (s, 3H), 2.71 (s, 3H); 13C-NMR (101 MHz, Chloroform-d) δ 162.92, 159.71, 158.99, 158.67, 155.58, 138.96, 134.44, 133.70, 130.67, 130.58, 129.73, 129.53, 127.30, 127.01, 113.93, 112.98, 55.25, 42.46, 36.34, 12.30; HRMS (m/z): calcd. for C22H20ClN4O3S (M + H+) 455.09446, found 455.07662.