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Vol. 49, No. 12
258 °C (EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 2.33 (3H, s), 3.80 (3H, s),
6.82 (1H, d, Jϭ6.8 Hz), 6.85—6.89 (1H, m), 7.06—7.16 (2H, m), 7.26 (2H,
d, Jϭ7.2 Hz), 7.63 (2H, d, Jϭ7.2 Hz), 7.72 (1H, t, Jϭ4.8 Hz), 7.76—7.90
(2H, m), 9.10 (2H, d, Jϭ4.8 Hz). FAB-MS m/z: 510 (Mϩϩ1).
Jϭ4.8 Hz). FAB-MS m/z: 524 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,6-diethylphenyl)ethenesulfonamide (5q): 560 mg (35%), mp 181—
1
182 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 0.98 (6H, t, Jϭ7.6 Hz),
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2-chlorophenyl)ethenesulfonamide (5d): 2.98 g (74%), mp 196—
2.53 (4H, q, Jϭ7.6 Hz), 3.81 (3H, s), 6.85—6.90 (1H, m), 6.77 (1H, d,
Jϭ7.6 Hz), 7.23 (1H, t, Jϭ7.6 Hz), 7.36 (1H, d, Jϭ15.6 Hz), 7.63 (1H, t,
Jϭ4.8 Hz), 7.95 (1H, d, Jϭ15.6 Hz), 8.94 (2H, d, Jϭ4.8 Hz). FAB-MS m/z:
552 (Mϩϩ1).
1
197 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 3.81 (3H, s), 6.81—6.90
(2H, m), 7.06—7.11 (1H, m), 7.12—7.16 (1H, m), 7.42—7.50 (2H, m),
7.56—7.59 (1H, m), 7.69 (1H, t, Jϭ4.8 Hz), 7.94 (1H, dd, Jϭ1.0, 7.5 Hz),
7.97—8.03 (2H, m), 9.02 (2H, d, Jϭ4.8 Hz). FAB-MS m/z: 528 (MϩϪ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(3-chlorophenyl)ethenesulfonamide (5e): 1.27 g (84%), mp 208—
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,6-dichlorophenyl)ethenesulfonamide (5r): 369 (76%), mp 197—
1
199 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 3.81 (3H, s), 6.79 (1H,
dd, Jϭ1.6, 8.0 Hz), 6.84—6.89 (1H, m), 7.06—7.11 (1H, m), 7.13 (1H, dd,
Jϭ1.8, 8.0 Hz), 7.39—7.44 (1H, m), 7.55 (1H, d, Jϭ8.0 Hz), 7.63 (1H, t,
Jϭ4.8 Hz), 7.87 (1H, d, Jϭ15.2 Hz), 7.94 (1H, d, Jϭ15.2 Hz), 8.93 (2H, d,
Jϭ4.8 Hz). FAB-MS m/z: 564 (Mϩϩ1).
1
210 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 3.81 (3H, s), 6.82 (1H,
dd, Jϭ1.6, 8.0 Hz), 6.84—6.89 (1H, m), 7.06—7.11 (1H, m), 7.13 (1H, dd,
Jϭ1.6, 8.0 Hz), 7.46—7.52 (2H, m), 7.69—7.75 (2H, m), 7.85—7.89 (2H,
m), 7.98 (1H, d, Jϭ15.6 Hz), 9.09 (2H, d, Jϭ4.8 Hz). FAB-MS m/z: 530
(Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,4,6-trimethylphenyl)ethenesulfonamide (5s): 1.23 g (80%), mp
1
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(4-chlorophenyl)ethenesulfonamide (5f): 1.11 g (73%), mp 244—
212—214 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 2.23 (3H, s), 2.25
(6H, s), 3.80 (3H, s), 6.80—6.83 (1H, m), 6.85—6.90 (1H, m), 6.92 (2H, s),
7.07—7.12 (1H, m), 7.13—7.16 (1H, m), 7.54 (1H, d, Jϭ16.0 Hz), 7.65
(1H, t, Jϭ4.8 Hz), 7.84 (1H, d, Jϭ16.0 Hz), 8.97 (2H, d, Jϭ4.8 Hz). FAB-
MS m/z: 538 (Mϩϩ1).
1
245 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 3.80 (3H, s), 6.81—6.83
(1H, m), 6.84—6.89 (1H, m), 7.06—7.15 (2H, m), 7.53 (2H, d, Jϭ8.4 Hz),
7.71 (1H, t, Jϭ4.8 Hz), 7.79 (2H, d, Jϭ8.4 Hz), 7.85—7.95 (2H, m), 9.09
(2H, d, Jϭ4.8 Hz). FAB-MS m/z: 530 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-1-methyl-2-phenylethenesulfonamide (5t): 1.05 g (81%), mp 203—
204 °C (EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 2.20 (3H, s), 3.81 (3H, s),
6.82 (1H, d, Jϭ7.6 Hz), 6.85—6.91 (1H, m), 7.08 (1H, d, Jϭ8.0 Hz), 7.10—
7.16 (1H, m), 7.36—7.47 (6H, m), 7.65 (1H, s), 7.97 (1H, br s), 8.91—9.00
(2H, m). FAB-MS m/z: 510 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-1-ethyl-2-phenylethenesulfonamide (5u): 886 mg (59%), mp 194—
195 °C (EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 1.12—1.22 (3H, m),
2.60—2.74 (2H, m), 3.81 (3H, s), 6.79 (1H, d, Jϭ7.2 Hz), 6.88 (1H, t,
Jϭ7.6 Hz), 7.09 (1H, t, Jϭ7.6 Hz), 7.14 (1H, d, Jϭ7.6 Hz), 7.36—7.46 (5H,
m), 7.65 (1H, s), 7.90—8.10 (1H, m), 8.91—9.02 (2H, m), 11.99 (1H, br s).
FAB-MS m/z: 524 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(4-ethylphenyl)ethenesulfonamide (5g): 1.11 g (62%), mp 258—
1
259 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 1.17 (3H, t, Jϭ7.7 Hz),
2.62 (2H, q, Jϭ7.7 Hz), 3.80 (3H, s), 6.79—6.91 (2H, m), 7.05—7.16 (2H,
m), 7.29 (2H, d, Jϭ8.1 Hz), 7.65 (2H, d, Jϭ8.1 Hz), 7.72 (1H, t, Jϭ4.5 Hz),
7.79—7.91 (2H, m), 9.11 (2H, d, Jϭ4.5 Hz). FAB-MS m/z: 524 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(4-tert-butylphenyl)ethenesulfonamide (5h): 1.05 g (67%), mp 259—
260 °C (EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 1.27 (9H, s), 3.80 (3H, s),
6.82 (1H, d, Jϭ7.6 Hz), 6.85—6.91 (1H, m), 7.06—7.16 (2H, m), 7.47 (2H,
d, Jϭ8.8 Hz), 7 .68 (2H, d, Jϭ8.8 Hz), 7.74 (1H, t, Jϭ4.8 Hz), 7.83 (1H, d,
Jϭ14.4 Hz), 7.91 (1H, d, Jϭ14.4 Hz), 9.13 (2H, d, Jϭ4.8 Hz). FAB-MS m/z:
552 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-phenyl-1-propylethenesulfonamide (5v): 1.11 g (72%), mp 156—
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(4-methoxyphenyl)ethenesulfonamide (5i): 1.02 g (68%), mp 227—
230 °C (EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 3.80 (6H, s), 6.81 (1H, d,
Jϭ8.0 Hz), 6.84—6.89 (1H, m), 7.01 (2H, d, Jϭ8.8 Hz), 7.06—7.11 (1H,
m), 7.12—7.16 (1H, m), 7.68—7.75 (4H, m), 7.81—7.88 (1H, m), 9.11 (2H,
d, Jϭ4.8 Hz). FAB-MS m/z: 526 (Mϩϩ1).
1
157 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 0.85 (3H, t, Jϭ7.6 Hz),
1.55—1.63 (2H, m), 2.54—2.66 (2H, m), 3.81 (3H, s), 6.78 (1H, d,
Jϭ7.6 Hz), 6.87 (1H, t, Jϭ7.6 Hz), 7.07—7.11 (1H, m), 7.14 (1H, d,
Jϭ8.0 Hz), 7.38—7.43 (5H, m), 7.65 (1H, s), 8.02 (1H, br s), 8.89—9.01
(2H, m). FAB-MS m/z: 538 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(4-trifluoromethylphenyl)ethenesulfonamide (5j): 2.18 g (70%), mp
212—213 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 3.81 (3H, s), 6.83
(1H, dd, Jϭ1.6, 8.0 Hz), 6.84—6.90 (1H, m), 7.03—7.12 (1H, m), 7.13—
7.16 (1H, m), 7.72 (1H, t, Jϭ4.8 Hz), 7.83 (2H, d, Jϭ8.0 Hz), 7.92—8.01
(3H, m), 8.05 (1H, d, Jϭ15.6 Hz), 9.11 (2H, d, Jϭ4.8 Hz). FAB-MS m/z:
564 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-methyl-2-phenylethenesulfonamide (5w): 915 mg (71%), mp Ͼ300 °C
(EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 2.48 (3H, s), 3.80 (3H, s),
6.81—6.90 (3H, m), 7.05—7.15 (2H, m), 7.20—7.35 (1H, m), 7.40—7.45
(2H, m), 7.61—7.68 (3H, m), 9.08 (2H, d, Jϭ4.8 Hz). FAB-MS m/z: 510
(Mϩϩ1).
1
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-1-methyl-2-(2,4,6-trimethylphenyl)ethenesulfonamide (5x): 1.35 g (86%),
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,3-dimethylphenyl)ethenesulfonamide (5m): 954 mg (64%), mp
1
mp 204—205 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 1.84 (6H, s),
1
211—212 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 2.22 (3H, s), 2.26
2.19 (3H, s), 2.35 (3H, s), 3.80 (3H, s), 6.80—6.92 (4H, m), 7.05—7.17
(2H, m), 7.62 (1H, s), 7.71—7.81 (1H, m), 8.86—9.02 (2H, m). FAB-MS
m/z: 552 (Mϩϩ1).
(3H, s), 3.80 (3H, s), 6.82 (1H, dd, Jϭ1.4, 8.4 Hz), 6.84—6.90 (1H, m),
7.06—7.18 (3H, m), 7.24 (1H, d, Jϭ7.4 Hz), 7.55 (1H, d, Jϭ7.4 Hz), 7.69
(1H, t, Jϭ4.4 Hz), 7.76 (1H, d, Jϭ15.1 Hz), 8.01 (1H, d, Jϭ15.1 Hz), 9.02
(2H, d, Jϭ4.4 Hz). FAB-MS m/z: 524 (Mϩϩ1).
Methyl (E)-4-(2-{N-[6-Chloro-5-(2-methoxyphenoxy)-2-(2-pyrim-
idinyl)pyrimidin-4-yl]sulfamoyl}ethenyl)benzoate (5k) To an ice-cooled
solution of methyl (E)-4-(2-sulfamoylethenyl)benzoate (4k) (650 mg,
2.69 mmol) in DMF (10 ml) was added 60% sodium hydride in mineral oil
(220 mg, 5.50 mmol), and the mixture was stirred for 10 min at room tem-
perature. To the mixture 4,6-dichloro-5-(2-methoxyphenoxy)pyrimidine (3)
(900 mg, 2.58 mmol) was added, and the mixture was stirred for 15 h at
room temperature. To the mixture was added 60% sodium hydride in min-
eral oil (60 mg, 1.50 mmol), and the mixture was stirred at room temperature
for 4 h. It was poured into ice-water and acidified with 1 M aqueous HCl. The
resulting precipitate was collected by filtration to give a mixture of 5k and
(E)-4-(2-{N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrim-
idinyl]sulfamoyl}ethenyl)benzoic acid (5l). All of the obtained mixture
(5k, l) and concentrated sulfuric acid (0.2 ml, 3.76 mmol) in MeOH (30 ml)
were heated under reflux for 24 h. It was then concentrated in vacuo and
water was added to the residue. The resulting precipitate was collected by
filtration. It was recrystallized from MeOH to give 5k (925 mg, 65%), mp
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,4-dimethylphenyl)ethenesulfonamide (5n): 985 mg (66%), mp
1
222—223 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 2.28 (3H, s), 2.32
(3H, s), 3.80 (3H, s), 6.83 (1H, dd, Jϭ1.6, 8.0 Hz), 6.88 (1H, dt, Jϭ1.6,
8.0 Hz), 7.06—7.16 (4H, m), 7.65 (1H, d, Jϭ8.0 Hz), 7.71 (1H, t,
Jϭ4.8 Hz), 7.80—7.90 (2H, m), 9.04 (2H, d, Jϭ4.8 Hz). FAB-MS m/z: 524
(Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,5-dimethylphenyl)ethenesulfonamide (5o): 930 mg (62%), mp
1
144—145 °C (EtOH), 400 MHz H-NMR (DMSO-d6) d: 2.26 (3H, s), 2.30
(3H, s), 3.80 (3H, s), 6.81—6.89 (2H, m), 7.06—7.11 (1H, m), 7.12—7.17
(1H, m), 7.55 (1H, s), 7.71 (1H, t, Jϭ5.2 Hz), 7.81—7.90 (2H, m), 9.04 (2H,
d, Jϭ5.2 Hz). FAB-MS m/z: 524 (Mϩϩ1).
(E)-N-[6-Chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-
yl]-2-(2,6-dimethylphenyl)ethenesulfonamide (5p): 1.02 g (68%), mp 214—
215 °C (EtOH), 400 MHz 1H-NMR (DMSO-d6) d: 2.26 (6H, s), 3.80 (3H, s),
6.80—6.84 (1H, m), 6.86—6.91 (1H, m), 7.06—7.19 (5H, m), 7.54 (1H, d,
Jϭ16.0 Hz), 7.64 (1H, t, Jϭ4.8 Hz), 7.87 (1H, d, Jϭ16.0 Hz), 8.95 (2H, d,
1
135—138 °C, 400 MHz H-NMR (DMSO-d6) d: 3.81 (3H, s), 3.87 (3H, s),
6.82 (1H, dd, Jϭ1.6, 8.0 Hz), 6.86 (1H, dt, Jϭ1.6, 8.0 Hz), 7.06—7.11 (1H,
m), 7.13 (1H, dd, Jϭ1.2, 8.0 Hz), 7.72 (1H, t, Jϭ5.2 Hz), 7.88—7.92 (2H,