JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
1243
water was added to quench the reaction. The mixture was 2H), 6.37–6.28 (m, 1H), 6.18 (d, J ¼ 17.1 Hz, 1H), 5.70 (d, J ¼ 9.9 Hz,
extracted with DCM to afford the crude product. The crude resi- 1H), 3.82 (d, J ¼ 6.0 Hz, 2H). MS (EI) m/z 357.1 [M þ Na]þ.
due was recrystallization to afford target compounds 5a-m.
2.1.3.9. N-(4-(N-(3-Fluorobenzyl)sulfamoyl)phenyl)acrylamide (5i).
1
2.1.3.1. N-(4-(N-Benzylsulfamoyl)phenyl)acrylamide (5a). White White solid. Yield 80%. Mp 152–154 ꢁC. H NMR (300 MHz, DMSO-
solid. Yield 75%. Mp 116–118 ꢁC. 1H NMR (300 MHz, DMSO-d6) d d6) d 10.39 (s, 1H), 8.01 (t, J ¼ 6.3 Hz, 1H), 7.70 (d, J ¼ 8.4 Hz, 2H),
10.50 (s, 1H), 8.02 (t, J ¼ 6.2 Hz, 1H), 7.81 (d, J ¼ 8.7 Hz, 2H), 7.72 (d, 7.61 (d, J ¼ 5.7 Hz, 2H), 7.22–7.15 (m, 1H), 6.95–6.89 (m, 3H),
J ¼ 8.7 Hz, 2H), 7.27–7.16 (m, 5H), 6.48–6.39 (m, 1H), 6.28 (d,
J ¼ 15.6 Hz, 1H), 5.79 (d, J ¼ 9.9 Hz, 1H), 3.92 (d, J ¼ 6.0 Hz, 2H). MS
(EI) m/z 315.1 [M-H]ꢂ.
6.37–6.28 (m, 1H), 6.18 (d, J ¼ 16.8 Hz, 1H), 5.69 (d, J ¼ 9.9 Hz, 1H),
3.87 (d, J ¼ 6.3 Hz, 2H). MS (EI) m/z 357.1 [M þ Na]þ.
2.1.3.10. N-(4-(N-(2-Chlorobenzyl)sulfamoyl)phenyl)acrylamide (5j).
1
White solid. Yield 78%. Mp 178–180 ꢁC. H NMR (300 MHz, DMSO-
2.1.3.2.
N-(4-(N-(4-Methoxybenzyl)sulfamoyl)phenyl)acrylamide
(5b). White solid. Yield 81%. Mp 156–158 ꢁC. 1H NMR (300 MHz,
DMSO-d6) d 10.38 (s, 1H), 7.82 (t, J ¼ 6.0 Hz, 1H), 7.70 (d, J ¼ 8.7 Hz,
2H), 7.61 (d, J ¼ 8.7 Hz, 2H), 7.00 (d, J ¼ 8.4 Hz, 4H), 6.69 (d,
J ¼ 8.7 Hz, 2H), 6.38–6.29 (m, 1H), 6.18 (d, J ¼ 17.1 Hz, 1H), 5.69 (d,
J ¼ 9.9 Hz, 1H), 3.75 (d, J ¼ 6.0 Hz, 2H), 3.57 (s, 3H). MS (EI) m/z
345.2 [M-H]ꢂ.
d6) d 10.41 (s, 1H), 8.00 (s, 1H), 7.71 (d, J ¼ 7.5 Hz, 2H), 7.64 (d,
J ¼ 8.7 Hz, 2H), 7.28–7.15 (m, 4H), 6.39–6.29 (m, 1H), 6.18 (d,
J ¼ 17.4 Hz, 1H), 5.69 (d, J ¼ 2.7 Hz, 1H), 3.91 (d, J ¼ 4.5 Hz, 2H). MS
(EI) m/z 349.1 [M-H]ꢂ.
2.1.3.11. N-(4-(N-(4-Bromobenzyl)sulfamoyl)phenyl)acrylamide (5k).
1
White solid. Yield 83%. Mp 194–196 ꢁC. H NMR (300 MHz, DMSO-
d6) d 10.44 (s, 1H), 7.98 (t, J ¼ 6.2 Hz, 1H), 7.71 (d, J ¼ 8.4 Hz, 2H),
7.61 (d, J ¼ 8.7 Hz, 2H), 7.34 (d, J ¼ 7.8 Hz, 2H), 7.07 (d, J ¼ 7.8 Hz,
2H), 6.38–6.29 (m, 1H), 6.17 (d, J ¼ 15.9 Hz, 1H), 5.69 (d, J ¼ 10.2 Hz,
1H), 3.80 (d, J ¼ 6.3 Hz, 2H). MS (EI) m/z 393.1, 395.1 [M-H]ꢂ.
2.1.3.3. N-(4-(N-(4-Chlorobenzyl)sulfamoyl)phenyl)acrylamide (5c).
White solid. Yield 80%. Mp 190–192 ꢁC. 1H NMR (300 MHz, DMSO-
d6) d 10.40 (s, 1H), 7.98 (t, J ¼ 6.3 Hz, 1H), 7.70 (d, J ¼ 8.4 Hz, 2H),
7.61 (d, J ¼ 8.4 Hz, 2H), 7.17 (dd, J ¼ 8.4, 8.1 Hz, 4H), 6.37–6.28 (m,
1H), 6.18 (d, J ¼ 16.5 Hz, 1H), 5.69 (d, J ¼ 2.7 Hz, 1H), 3.82 (d,
J ¼ 6.0 Hz, 2H). MS (EI) m/z 349.1 [M-H]ꢂ.
2.1.3.12. N-(4-(N-(3-Bromobenzyl)sulfamoyl)phenyl)acrylamide (5l).
1
White solid. Yield 81%. Mp 156–158 ꢁC. H NMR (300 MHz, DMSO-
d6) d 10.40 (s, 1H), 8.01 (t, J ¼ 6.0 Hz, 1H), 7.70 (d, J ¼ 8.4 Hz, 2H),
7.60 (d, J ¼ 8.7 Hz, 2H), 7.26 (s, 2H), 7.11 (d, J ¼ 3.9 Hz, 2H),
6.38–6.29 (m, 1H), 6.18 (d, J ¼ 15.9 Hz, 1H), 5.69 (d, J ¼ 10.2 Hz, 1H),
3.86 (d, J ¼ 6.0 Hz, 2H). MS (EI) m/z 393.1, 395.1 [M-H]ꢂ.
2.1.3.4. N-(4-(N-(3-Chlorobenzyl)sulfamoyl)phenyl)acrylamide (5d).
White solid. Yield 51%. Mp 157–159 ꢁC. 1H NMR (300 MHz, DMSO-
d6) d 10.58 (s, 1H), 8.15 (s, 1H), 7.83 (dd, J ¼ 9.0, 3.2 Hz, 2H),
7.78–7.65 (m, 2H), 7.47–7.06 (m, 4H), 6.44 (dd, J ¼ 9.8, 3.4 Hz, 1H),
6.37–6.22 (m, 1H), 5.88 –5.74 (m, 1H), 3.99 (d, J ¼ 3.3 Hz, 2H). 13C
NMR (126 MHz, DMSO) d 164.08, 142.99, 140.90, 135.28, 133.36,
131.94, 130.53, 128.38, 128.13, 127.79, 127.47, 126.65, 119.53,
45.86. MS (EI) m/z 349.1 [M-H]ꢂ.
2.1.3.13. N-(4-(N-(3,4-Dichlorobenzyl)sulfamoyl)phenyl)acrylamide
(5m). White solid. Yield 82%. Mp 148–150 ꢁC. 1H NMR (300 MHz,
DMSO-d6) d 10.41 (s, 1H), 8.05 (s, 1H), 7.65 (d, J ¼ 29.4 Hz, 4H), 7.34
(d, J ¼ 30.0 Hz, 2H), 7.11 (s, 1H), 6.38–6.15 (m, 2H), 5.70 (s, 1H),
3.82 (d, J ¼ 6.0 Hz, 2H). MS (EI) m/z 383.1 [M-H]ꢂ.
2.1.3.5. N-(4-(N-Phenethylsulfamoyl)phenyl)acrylamide (5e). White
solid. Yield 75%. Mp 154–156 ꢁC. 1H NMR (300 MHz, DMSO-d6) d
10.39 (s, 1H), 7.70 (d, J ¼ 8.1 Hz, 2H), 7.61 (d, J ¼ 7.5 Hz, 2H), 7.49 (s,
1H), 7.09 (m, 4H), 6.37–6.28 (m, 1H), 6.17 (d, J ¼ 15.6 Hz, 1H), 5.69
(d, J ¼ 8.7 Hz, 1H), 2.80 (s, 1H), 2.53 (s, 1H). MS (EI) m/z
353.1 [M þ Na]þ.
2.1.4. General preparation of N-phenylacrylamide 6
To a solution of aniline (0.043 mol) in DCM (50 ml) was added TEA
(0.086 mol). Then acryloyl chloride (0.047 mol) was added dropwise
to the mixture at 0 ꢁC for 0.5 h. The reaction was allowed to stir at
rt overnight. After the reaction was completed, the water was
added to quench the reaction. The mixture was extracted with
DCM to afford the crude product that was purified by flash col-
umn chromatography on silica gel to afford N-phenylacrylamide 6
(white solid, Yield 72.8%)40. 1H NMR (300 MHz, Chloroform-d) d
10.14 (s, 1H), 7.67 (d, J ¼ 8.1 Hz, 2H), 7.32 (t, J ¼ 7.8 Hz, 2H), 7.07 (t,
J ¼ 7.2 Hz, 1H), 6.44 (dd, J ¼ 16.8, 9.9 Hz, 1H), 6.26 (dd, J ¼ 16.8,
1.5 Hz, 1H), 5.75 (dd, J ¼ 9.9, 1.5 Hz, 1H).
2.1.3.6. N-(4-(N-(4-(Trifluoromethyl)benzyl)sulfamoyl)phenyl) acryl-
amide (5f). White solid. Yield 80%. Mp 198–200 ꢁC. 1H NMR
(300 MHz, DMSO-d6) d 10.38 (s, 1H), 8.07 (s, 1H), 7.69 (d, J ¼ 7.8 Hz,
2H), 7.61 (d, J ¼ 8.1 Hz, 2H), 7.50 (d, J ¼ 7.2 Hz, 4H), 7.33 (d,
J ¼ 7.2 Hz, 2H), 6.37–6.15 (m, 1H), 6.18 (d, J ¼ 16.5 Hz, 1H), 5.69 (d,
J ¼ 9.9 Hz, 1H), 3.94 (d, J ¼ 4.5 Hz, 2H). MS (EI) m/z 407.1 [M þ Na]þ.
2.1.3.7. N-(4-(N-(3-(Trifluoromethyl)benzyl)sulfamoyl)phenyl) acryl-
amide (5g). White solid. Yield 77%. Mp 152–154 ꢁC. 1H NMR
(300 MHz, DMSO-d6) d 10.55 (s, 1H), 8.19 (t, J ¼ 6.2 Hz, 1H), 7.79 (d,
J ¼ 8.7 Hz, 2H), 7.69 (d, J ¼ 8.7 Hz, 2H), 7.55–7.44 (m, 4H), 6.49–6.40
(m, 1H), 6.27 (d, J ¼ 16.8 Hz, 1H), 5.78 (d, J ¼ 3.9 Hz, 1H), 4.06 (d,
J ¼ 6.0 Hz, 2H). MS (EI) m/z 383.1 [M-H]ꢂ.
2.1.5. General preparation of 4-acrylamidobenzenesulfonyl chlor-
ide 7
N-phenylacrylamide (0.031 mol) was added slowly to sulphuryl
chloride (15 ml) at 0 ꢁC for more than 0.5 h. The reaction was
stirred at 70 ꢁC for 1 h. After the reaction was completed, the mix-
ture was poured into ice water slowly to quench the reaction. The
2.1.3.8. N-(4-(N-(4-Fluorobenzyl)sulfamoyl)phenyl)acrylamide (5h).
White solid. Yield 82%. Mp 178–180 ꢁC. 1H NMR (300 MHz, DMSO- mixture was stirred at rt for 1 h and the solid was filtered-off and
d6) d 10.40 (s, 1H), 7.95 (t, J ¼ 6.0 Hz, 1H), 7.70 (d, J ¼ 8.7 Hz, 2H), washed with water (2 ꢃ 50 ml). The crude solid was dissolved in
7.61 (d, J ¼ 8.4 Hz, 2H), 7.14 (t, J ¼ 6.8 Hz, 1H), 6.97 (t, J ¼ 8.6 Hz, CH2Cl2 (50 ml), the organic layer was washed with brine, and the