24
L. Pan et al. / European Journal of Medicinal Chemistry 50 (2012) 18e26
OCH2CH3), 7.151 (d, 1H, JH ¼ 5.2 Hz, pyrim-H5), 7.694 (d, 1H,
JH ¼ 8.8 Hz, Ar-H), 8.130 (d, 1H, JH ¼ 8.4 Hz, Ar-H), 8.577 (d, 1H,
JH ¼ 4.8 Hz, pyrim-H6), 8.503 (s, 1H, Ar-H), 10.787 (s, 1H, CONH-
pyrim), 11.287 (s, 1H, CONH-Ar), 13.433 (br, 1H, SO2NH). 13C NMR
pyrim-H6), 10.434 (s, 1H, CONH-Ar), 10.873 (br, 1H, CONH-pyrim),
13.472 (br, 1H, SO2NH). 13C NMR (300 MHz, DMSO-d6)
(ppm):
d
23.941, 54.431, 102.652, 119.273, 121.850, 123.287, 124.085, 131.883,
138.385, 150.018, 155.212, 156.310, 168.869, 170.169. ESI-FTICR-MS
for C14H14ClN5O5S: found 422.0297 [M þ Na]þ, calcd 422.0296
[M þ Na]þ (error 0.237 ppm).
(400 MHz, DMSO-d6)
d (ppm): 13.800, 23.501, 62.593, 109.504,
115.687, 123.555, 125.200, 126.116, 132.208, 136.912, 148.825,
155.814, 156.453, 157.284, 159.883, 168.863. ESI-FTICR-MS for
C16H16ClN5O6S: found 464.0397 [M þ Na]þ, calcd 464.0402
[M þ Na]þ (error 1.078 ppm).
2-Chloro-N-(4-chloro-3-(N-(4-methoxypyrimidin-2-ylcarbamoyl)
sulfamoyl)phenyl)acetamide (10o)
White solid, yield 91%, m.p. 188e189 ꢀC; 1H NMR (400 MHz,
N-(4-chloro-3-(N-(4-methylpyrimidin-2-ylcarbamoyl)sulfamoyl)
phenyl)-2,2,3,3,4,4,4-heptafluorobutanamide (10j)
DMSO-d6) d (ppm): 3.995 (s, 3H, pyrim-OCH3), 4.305 (s, 2H,
COCH2Cl), 6.685 (d, 1H, JH ¼ 6.0 Hz, pyrim-H5), 7.607 (d, 1H,
JH ¼ 8.0 Hz, Ar-H), 7.953 (d, 1H, JH ¼ 8.4 Hz, Ar-H), 8.346e8.371 (m,
2H, Ar-H and pyrim-H6), 10.816 (s, 1H, CONH-Ar), 10.931 (br, 1H,
CONH-pyrim), 13.499 (br, 1H, SO2NH). 13C NMR (400 MHz, DMSO-
White solid, yield 80%, m.p. 181e182 ꢀC; 1H NMR (400 MHz,
DMSO-d6)
d (ppm): 2.469 (s, 3H, pyrim-CH3), 7.160 (d, 1H,
JH ¼ 5.2 Hz, pyrim-H5), 7.756 (d, 1H, JH ¼ 8.8 Hz, Ar-H), 8.112 (d,
1H, JH ¼ 8.0 Hz, Ar-H), 8.555 (s, 1H, Ar-H), 8.578 (d, 1H,
JH ¼ 5.2 Hz, pyrim-H6), 10.834 (s, 1H, CONH-pyrim), 11.810 (s, 1H,
CONH-Ar), 13.507 (br, 1H, SO2NH). 13C NMR (400 MHz, DMSO-d6)
d6)
d (ppm): 43.442, 54.570, 102.690, 119.653, 122.224, 123.291,
124.281, 132.045, 137.534, 150.421, 156.046, 156.542, 165.196,
170.338. ESI-FTICR-MS for C14H13Cl2N5O5S: found 455.9899
[M þ Na]þ, calcd 455.9907 [M þ Na]þ (error 1.754 ppm).
N-(4-chloro-3-(N-(4-methoxypyrimidin-2-ylcarbamoyl)sulfa-
moyl)phenyl)isobutyramide (10p)
d
(ppm): 23.490, 107.865, 109.427, 115.175, 115.666, 121.609,
124.250, 126.601, 126.758, 132.495, 135.578, 148.971, 155.461,
156.369, 157.126, 168.994. MALDI-FTICR-MS for C16H11ClF7N5O4S:
found 538.0183 [M þ H]þ, calcd 538.0181 [M þ H]þ (error
0.372 ppm).
Yellow solid, yield 68%, m.p. 137e139 ꢀC; 1H NMR (400 MHz,
DMSO-d6)
d
(ppm): 1.124 (d, 6H, JH ¼ 6.4 Hz, isopropyl-CH3),
N-(4-chloro-3-(N-(4-methylpyrimidin-2-ylcarbamoyl)sulfamoyl)
phenyl)benzamide (10k)
2.602e2.667 (m, 1H, isopropyl-CH), 3.959 (s, 3H, pyrim-OCH3),
6.696 (d, 1H, JH ¼ 6.0 Hz, pyrim-H5), 7.578 (d, 1H, JH ¼ 8.8 Hz, Ar-H),
7.987 (d, 1H, JH ¼ 7.6 Hz, Ar-H), 8.377 (d, 1H, JH ¼ 6.0 Hz, pyrim-H6),
8.460 (s, 1H, Ar-H), 10.408 (s, 1H, CONH-Ar), 10.922 (br, 1H, CONH-
White solid, yield 85%, m.p. 262e263 ꢀC; 1H NMR (400 MHz,
DMSO-d6)
d (ppm): 2.468 (s, 3H, pyrim-CH3), 7.151 (d, 1H,
JH ¼ 4.8 Hz, pyrim-H5), 7.547e7.691 (m, 4H, Ar-H), 8.005e8.024
(m, 2H, Ar-H), 8.232 (d, 1H, JH ¼ 8.4 Hz, Ar-H), 8.583 (d, 1H,
JH ¼ 4.8 Hz, pyrim-H6), 8.687 (s, 1H, Ar-H), 10.758 (s, 2H, CONH-
Ar and CONH-pyrim), 13.421 (br, 1H, SO2NH). 13C NMR (400 MHz,
pyrim). 13C NMR (400 MHz, DMSO-d6)
d (ppm): 19.297, 35.015,
54.492, 102.720, 119.412, 121.988, 123.232, 124.251, 131.851,
138.528, 150.006, 154.985, 156.223, 170.216, 175.801. MALDI-FTICR-
MS for C16H18ClN5O5S: found 428.0793 [M þ H]þ, calcd 428.0790
[M þ H]þ (error 0.701 ppm).
DMSO-d6)
d (ppm): 23.498, 109.433, 115.667, 123.192, 123.879,
125.762, 127.734, 127.774, 128.449, 132.019, 134.080, 138.550,
148.822, 156.514, 157.396, 165.889, 168.795. ESI-FTICR-MS for
C19H16ClN5O4S: found 468.0500 [M þ Na]þ, calcd 468.0504
[M þ Na]þ (error 0.855 ppm).
N-(4-chloro-3-(N-(4-methoxypyrimidin-2-ylcarbamoyl)sulfa-
moyl)phenyl)cyclopropanecarboxamide (10q)
White solid, yield 86%, m.p. 140e141 ꢀC; 1H NMR (400 MHz,
DMSO-d6)
d
(ppm): 0.841 (d, 4H, JH ¼ 6.4 Hz, cyclopropyl-CH2),
N-(4-chloro-3-(N-(4-methylpyrimidin-2-ylcarbamoyl)sulfamoyl)
phenyl)-2,2,2-trifluoroacetamide (10l)
1.785e1.846 (m, 1H, cyclopropyl-CH), 3.951 (s, 3H, pyrim-OCH3),
6.690 (d, 1H, JH ¼ 6.0 Hz, pyrim-H5), 7.565 (d, 1H, JH ¼ 8.4 Hz, Ar-H),
7.927e7.955 (m, 1H, Ar-H), 8.367 (d, 1H, JH ¼ 6.4 Hz, pyrim-H6),
8.437 (d, 1H, JH ¼ 2.4 Hz, Ar-H), 10.778 (s, 1H, CONH-Ar), 10.918 (br,
Light yellow solid, yield 72%, m.p. 191e192 ꢀC; 1H NMR
(400 MHz, DMSO-d6)
d (ppm): 2.475 (s, 3H, pyrim-CH3), 7.165 (d,
1H, JH ¼ 4.8 Hz, pyrim-H5), 7.755 (d, 1H, JH ¼ 8.8 Hz, Ar-H), 8.098 (d,
1H, JH ¼ 8.8 Hz, Ar-H), 8.548 (s, 1H, Ar-H), 8.585 (d, 1H, JH ¼ 4.4 Hz,
pyrim-H6), 10.828 (br, 1H, CONH-pyrim), 11.775 (s, 1H, CONH-Ar),
1H, CONH-pyrim). 13C NMR (400 MHz, DMSO-d6)
d (ppm): 7.566,
14.595, 54.532, 102.790, 119.217, 121.850, 123.212, 124.149, 131.910,
138.436, 149.991, 154.806, 156.111, 170.275, 172.273. MALDI-FTICR-
MS for C16H16ClN5O5S: found 426.0629 [M þ H]þ, calcd 426.0633
[M þ H]þ (error 0.939 ppm).
13.512 (br, 1H, SO2NH). 13C NMR (300 MHz, DMSO-d6)
d (ppm):
23.485, 109.448, 113.562, 115.663, 124.014, 126.280, 126.557,
132.452, 135.746, 148.950, 154.115, 156.396, 157.161, 168.936. ESI-
FTICR-MS for C14H11ClF3N5O4S: found 460.0056 [M þ Na]þ, calcd
460.0064 [M þ Na]þ (error 1.739 ppm).
N-(4-chloro-3-(N-(4-methoxypyrimidin-2-ylcarbamoyl)sulfa-
moyl)phenyl)pivalamide (10r)
White solid, yield 88%, m.p. 130e132 ꢀC; 1H NMR (400 MHz,
N-(4-chloro-3-(N-(4-methylpyrimidin-2-ylcarbamoyl)sulfamoyl)
phenyl)formamide (10m)
DMSO-d6) d (ppm): 1.245 (s, 9H, CO-neopentyl), 3.953 (s, 3H,
pyrim-OCH3), 6.681 (d, 1H, JH ¼ 6.0 Hz, pyrim-H5), 7.571 (d, 1H,
JH ¼ 8.8 Hz, Ar-H), 8.088 (d, 1H, JH ¼ 8.4 Hz, Ar-H), 8.388 (d, 1H,
JH ¼ 4.0 Hz, pyrim-H6), 8.503 (s, 1H, Ar-H), 9.728 (s, 1H, CONH-Ar),
10.846 (br, 1H, CONH-pyrim), 13.446 (br, 1H, SO2NH). 13C NMR
Yellow solid, yield 46%, m.p. 180e181 ꢀC; 1H NMR (400 MHz,
DMSO-d6)
d (ppm): 2.468 (s, 3H, pyrim-CH3), 7.153 (d, 1H,
JH ¼ 4.8 Hz, pyrim-H5), 7.647 (d, 1H, JH ¼ 8.8 Hz, Ar-H), 7.940e7.967
(m, 1H, Ar-H), 8.385 (s, 1H, CHO), 8.459 (d, 1H, JH ¼ 2.0 Hz, Ar-H),
8.581 (d, 1H, JH ¼ 5.2 Hz, pyrim-H6), 10.714 (s, 1H, CONH-Ar),
10.799 (s, 1H, CONH-pyrim), 13.425 (br, 1H, SO2NH). 13C NMR
(400 MHz, CDCl3) d (ppm): 27.479, 39.834, 54.729,103.353,123.509,
125.710, 126.125, 132.287, 136.068, 137.540, 149.346, 156.502,
157.609, 170.602, 177.215. ESI-FTICR-MS for C17H20ClN5O5S: found
464.0759 [M þ Na]þ, calcd 464.0766 [M þ Na]þ (error 1.508 ppm).
N-(4-chloro-3-(N-(4-methoxypyrimidin-2-ylcarbamoyl)sulfa-
moyl)phenyl)acrylamide (10s)
(400 MHz, DMSO-d6)
d (ppm): 23.500, 109.455, 115.683, 122.095,
123.907, 124.889, 132.331, 137.427, 148.846, 156.424, 157.339,
160.236, 168.874. MALDI-FTICR-MS for C13H12ClN5O4S: found
392.0192 [M þ Na]þ, calcd 392.0191 [M þ Na]þ (error 0.255 ppm).
N-(4-chloro-3-(N-(4-methoxypyrimidin-2-ylcarbamoyl)sulfa-
moyl)phenyl)acetamide (10n)
White solid, yield 83%, m.p. 168e170 ꢀC; 1H NMR (400 MHz,
DMSO-d6)
d (ppm): 3.964 (s, 3H, pyrim-OCH3), 5.843 (d, 1H,
JH ¼ 9.6 Hz, CH]CH2), 6.308e6.476 (m, 2H, CH]CH2), 6.691 (d, 1H,
JH ¼ 4.0 Hz, pyrim-H5), 7.615 (d, 1H, JH ¼ 8.4 Hz, Ar-H), 8.075 (d, 1H,
JH ¼ 8.4 Hz, Ar-H), 8.380 (d, 1H, JH ¼ 4.0 Hz, pyrim-H6), 8.444 (s, 1H,
Ar-H),10.643 (s, 1H, CONH-Ar), 10.888 (br, 1H, CONH-pyrim),13.508
White solid, yield 82%, m.p. 189e190 ꢀC; 1H NMR (400 MHz,
DMSO-d6) d (ppm): 2.088 (s, 3H, COCH3), 3.953 (s, 3H, pyrim-OCH3),
6.683 (d, 1H, JH ¼ 5.6 Hz, pyrim-H5), 7.570 (d, 1H, JH ¼ 8.0 Hz, Ar-H),
7.957 (d, 1H, JH ¼ 8.4 Hz, Ar-H), 8.366e8.386 (m, 2H, Ar-H and
(br, 1H, SO2NH). 13C NMR (300 MHz, DMSO-d6)
d (ppm): 54.449,