Design and Activity of Anthranilic Diamides
1501
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-bromo-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18b
8.37 (s, 1H, NH), 8.19 (d, J 8.0, 1H, pyridine-H), 7.62 (dd, J1 8.0,
J2 4.0, 1H, pyridine-H), 7.48 (s, 1H, Ar-H), 7.39 (s, 2H, Ar-H,
pyrazole-H), 4.22 (s, 2H, CH2), 3.47 (s, 3H, N(O)¼SCH3), 2.19
(s, 3H, Ar-CH3), 1.44 (s, 6H, CH3). dC (400 MHz, [D6]DMSO)
166.1, 162.4, 155.5, 148.5, 147.0, 139.2, 138.4, 131.0, 127.9,
126.8, 126.6, 125.8, 112.4, 110.5, 58.9, 52.2, 42.6, 26.9, 26.8,
17.6. HRMS (MALDI) 647.9930, 649.0066, 649.9937,
651.0013, 651.9921, 653.0014 ([M þ Na]þ). Anal. Calc. for
C23H22BrCl2N7O3S: C 44.03, H 3.53, N 15.63. Found: C 43.88,
H 3.69, N 15.58.
White granules (83% yield), mp 125–1278C. nmax(KBr)/cmꢀ1
3277, 3063, 2988, 2924, 2358, 2196, 1672, 1533, 1466, 1371,
1305, 1249, 1197, 1030, 976, 868, 813, 759. dH (400 MHz, [D6]
DMSO) 10.20 (s, 1H, NH), 8.50 (d, J 4.4, 1H, pyridine-H), 8.31
(s, 1H, NH), 8.18 (d, J 8.0, 1H, pyridine-H), 7.62–7.64 (m, 2H,
pyridine-H, Ar-H), 7.50 (s, 1H, Ar-H), 7.34 (s, 1H, pyrazole-H),
4.22 (s, 2H, CH2), 3.47 (s, 3H, N(O)¼SCH3), 2.19 (s, 3H,
Ar-CH3), 1.44 (s, 6H, CH3). dC (400 MHz, [D6]DMSO) 166.4,
156.1, 149.0, 147.6, 140.1, 139.7, 139.5, 139.3, 137.2, 134.5,
132.0, 129.1, 128.4, 127.2, 119.8, 112.9, 107.7, 59.4, 52.8, 43.2,
27.4, 27.3, 18.0. Anal. Calc. for C23H22BrCl2N7O3S: C 44.03,
H 3.53, N 15.63. Found: C 43.88, H 3.87, N 15.56.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-chloro-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21a
White granules (68 % yield), mp 112–1148C. nmax(KBr)/
cmꢀ1 3272, 3068, 3006, 2925, 2363, 2197, 1670, 1534, 1466,
1370, 1304, 1252, 1198, 1134, 1032, 974, 878, 812, 758. dH
(400 MHz, [D6]DMSO) 10.29 (s, 1H, NH), 8.75 (s, 1H, NH),
8.51 (d, J 4.4, 1H, pyridine-H), 8.18 (d, J 8.0, 1H, pyridine-H),
7.62 (dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.53 (s, 1H, Ar-H), 7.43
(s, 1H, Ar-H), 7.36 (s, 1H, pyrazole-H), 3.72–3.80 (m, 2H, CH2),
3.63–3.64 (m, 2H, CH2), 3.49 and 3.00 (s, 3H, N(O)¼SCH3),
2.20 (s, 3H, Ar-CH3). dC (400 MHz, [D6]DMSO) 166.1, 155.7,
148.4, 147.1, 139.6, 139.3, 139.1, 138.6, 135.1, 131.6, 131.4,
130.8, 127.9, 126.6, 125.5, 112.4, 107.3, 52.9, 40.6, 33.0,
17.6. HRMS (MALDI) 576.0149, 577.0191, 578.0119,
579.0157, 580.0088, 581.0127 ([M þ Na]þ). Anal. Calc. for
C21H18Cl3N7O3S: C 45.46, H 3.27, N 17.67. Found: C 45.28,
H 3.52, N 17.52.
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-cyano-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18c
Colourless granules (71 % yield), mp 135–1378C. nmax(KBr)/
cmꢀ1 3284, 3064, 2994, 2890, 2354, 2194, 2056, 1996, 1686,
1534, 1468, 1370, 1253, 1150, 1035, 978, 884, 813, 758. dH
(400 MHz, [D6]DMSO) 10.44 (s, 1H, NH), 8.51 (d, J 4.4, 1H,
pyridine-H), 8.42 (s, 1H, NH), 8.19 (d, J 8.0, 1H, pyridine-H),
7.91 (s, 1H, Ar-H), 7.78 (s, 1H, Ar-H), 7.63 (dd, J1 8.0, J2 4.8,
1H, pyridine-H), 7.38 (s, 1H, pyrazole-H), 4.22 (s, 2H, CH2),
3.48 (s, 3H, N(O)¼SCH3), 2.26 (s, 3H, Ar-CH3), 1.44 (s, 6H,
CH3). dC (400 MHz, [D6]DMSO) 166.9, 156.6, 149.5, 148.3,
140.8, 140.5, 139.9, 138.8, 138.0, 136.5, 136.3, 131.3, 129.1,
127.9, 119.3, 113.6, 110.4, 108.7, 60.2, 53.5, 43.9, 28.1, 28.0,
18.8. HRMS (MALDI) 595.0804, 596.0848, 597.0783,
598.0828, 599.0790, 600.0830 ([M þ Na]þ). Anal. Calc. for
C24H22Cl2N8O3S: C 50.27, H 3.87, N 19.54. Found: C 50.13,
H 4.02, N 19.44.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-bromo-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21b
White powder (60 % yield), mp 123–1258C. nmax(KBr)/cmꢀ1
3276, 3068, 3007, 2927, 2358, 2197, 1674, 1533, 1466, 1369,
1303, 1253, 1196, 1133, 1032, 972, 864, 810, 759. dH (400 MHz,
[D6]DMSO) 10.30 (s, 1H, NH), 8.76 (br, 1H, NH), 8.52 (s, 1H,
pyridine-H), 8.18 (d, J 8.0, 1H, pyridine-H), 7.65 (s, 2H,
pyridine-H, Ar-H), 7.55 (s, 1H, Ar-H), 7.36 (s, 1H, pyrazole-
H), 3.76–3.77 (m, 1H, HA-CH2), 3.64–3.65 (m, 1H, HB-CH2),
3.55–3.56 (m, 1H, HC-CH2), 3.50 and 3.00 (s, 3H, N(O)¼
SCH3), 3.24–3.26 (m, 1H, HD-CH2), 2.20 (s, 3H, Ar-CH3). dC
(400 MHz, [D6]DMSO) 166.2, 156.1, 149.0, 147.6, 140.1,
139.8, 139.6, 139.3, 135.0, 134.9, 132.4, 128.8, 128.4, 127.1,
119.7, 112.9, 107.8, 53.4, 53.3, 41.1, 33.7, 33.5, 18.0. Anal.
Calc. for C21H18BrCl2N7O3S: C 42.09, H 3.03, N 16.36. Found:
C 41.97, H 3.28, N 16.28.
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-bromo-6-methylphenyl)-3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18d
White powder (56 % yield), mp 136–1388C. nmax(KBr)/cmꢀ1
3272, 3063, 2989, 2923, 2365, 2196, 1669, 1533, 1465, 1353,
1302, 1248, 1196, 1029, 966, 867, 813, 758. dH (400 MHz, [D6]
DMSO) 10.18 (s, 1H, NH), 8.50 (d, J 4.4, 1H, pyridine-H), 8.31
(s, 1H, NH), 8.18 (d, J 8.0, 1H, pyridine-H), 7.62–7.64 (m, 2H,
pyridine-H, Ar-H), 7.50 (s, 1H, Ar-H), 7.40 (s, 1H, pyrazole-H),
4.22 (s, 2H, CH2), 3.47 (s, 3H, N(O)¼SCH3), 2.19 (s, 3H, Ar-
CH3), 1.43 (s, 6H, CH3). dC (400 MHz, [D6]DMSO) 166.0,
155.4, 148.4, 147.1, 139.2, 139.1, 138.8, 136.7, 134.0, 131.5,
128.6, 127.9, 126.8, 126.6, 119.3, 112.4, 110.6, 58.9, 52.3, 42.7,
26.9, 26.8, 17.5. Anal. Calc. for C23H22Br2ClN7O3S: C 41.12,
H 3.30, N 14.59. Found: C 40.94, H 3.62, N 14.29.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-cyano-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21c
White granules (52 % yield), mp 200–2028C. nmax(KBr)/
cmꢀ1 3273, 3072, 2987, 2930, 2358, 2199, 1648, 1535, 1465,
1368, 1304, 1263, 1136, 1076, 1034, 970, 894, 811, 760. dH
(400 MHz, [D6]DMSO) 10.53 (s, 1H, NH), 8.79 (br, 1H, NH),
8.51 (d, J 4.0, 1H, pyridine-H), 8.18 (d, J 8.0, 1H, pyridine-H),
7.93 (s, 1H, Ar-H), 7.82 (s, 1H, Ar-H), 7.62 (dd, J1 7.6, J2 4.8,
1H, pyridine-H), 7.38 (s, 1H, pyrazole-H), 3.73–3.80 (m, 1H,
HA-CH2), 3.62–3.65 (m, 1H, HB-CH2), 3.53–3.56 (m, 1H,
HC-CH2), 3.48 and 2.99 (s, 3H, N(O)¼SCH3), 3.23–3.26 (m,
1H, HD-CH2), 2.26 (s, 3H, Ar-CH3). dC (400 MHz, [D6]DMSO)
165.8, 155.6, 148.3, 147.2, 139.7, 139.3, 138.8, 137.6, 137.0,
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-chloro-6-methylphenyl)-3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18e
White solid (57 % yield), mp 131–1328C. nmax(KBr)/cmꢀ1
3283, 3065, 2987, 2926, 2358, 2196, 1673, 1534, 1464, 1353,
1303, 1249, 1197, 1135, 1029, 965, 878, 812, 757. dH (400 MHz,
[D6]DMSO) 10.29 (s, 1H, NH), 8.50 (d, J 4.0, 1H, pyridine-H),