Z. Li, W. Xin, Q. Wang et al.
European Journal of Medicinal Chemistry 217 (2021) 113319
5.1.31. N-(3-(N-L-Leucylsulfamoyl)phenyl)-3,4-
dimethoxybenzamide (76)
Compound 76 (19.8 mg, 21.5% yield) was prepared from 26
(73 mg, 0.19 mmol) and 3,4-dimethoxybenzoic acid (38 mg,
0.21 mmol) following general procedure 2. 1H NMR (400 MHz,
(d, J ¼ 2.7 Hz,1H), 6.73 (dd, J ¼ 3.5,1.7 Hz,1H), 3.81 (s,1H),1.67e1.51
(m, 3H), 0.85 (dd, J ¼ 6.1, 2.3 Hz, 6H). 13C NMR (101 MHz, DMSO‑d6)
d 156.92, 147.44, 146.69, 139.70, 129.93, 125.33, 123.03, 119.25,
115.89, 112.72, 52.01, 23.88, 23.10, 21.91. Mp: 237e239 ꢂC. HRMS:
[MþH]þ calcd [C17H21N3O5SþH]þ 380.1280, found 380.1275. HPLC:
gradient A, 96.3% purity, 6.1 min.
DMSO‑d6)
d
10.57 (s, 1H), 8.54 (s, 1H), 8.34 (s, 3H), 8.13 (d, J ¼ 6.6 Hz,
1H), 7.69 (d, J ¼ 8.5 Hz, 1H), 7.63e7.59 (m, 2H), 7.09 (d, J ¼ 8.1 Hz,
1H), 4.01 (s, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 1.54 (s, 3H), 0.84 (s, 6H).
5.1.36. N-(3-(N-L-Leucylsulfamoyl)phenyl)thiophene-2-
carboxamide (81)
13C NMR (101 MHz, DMSO‑d6)
d 169.57, 165.66, 152.42, 148.79,
140.47, 129.83, 126.66, 125.65, 122.67, 121.90, 119.40, 111.67, 111.45,
56.20, 51.85, 23.89, 23.07, 22.07. Mp: 261e262 ꢂC. HRMS: [MþH]þ
calcd [C21H27N3O6SþH]þ 450.1699, found 450.1698. HPLC: gradient
A, 98.1% purity, 6.9 min.
Compound 81 (23 mg, 28.0% yield) was prepared from 26
(73 mg, 0.19 mmol) and thiophene-2-carboxylic acid (27 mg,
0.21 mmol) following general procedure 2. 1H NMR (400 MHz,
DMSO‑d6)
d
10.82 (s,1H), 8.53 (s,1H), 8.36 (s, 3H), 8.24 (d, J ¼ 3.6 Hz,
1H), 8.14 (d, J ¼ 8.1 Hz,1H), 7.90 (d, J ¼ 5.0 Hz,1H), 7.68 (d, J ¼ 7.9 Hz,
5.1.32. N-(3-(N-L-Leucylsulfamoyl)phenyl)-3,4,5-
trimethoxybenzamide (77)
1H), 7.62 (t, J ¼ 7.9 Hz, 1H), 7.28e7.23 (m, 1H), 3.87 (s, 1H), 1.67e1.51
(m, 3H), 0.89e0.80 (m, 6H). 13C NMR (101 MHz, DMSO‑d6)
d 169.57,
Compound 77 (25.3 mg, 32.7% yield) was prepared from 26
(59 mg, 0.15 mmol) and 3,4,5-trimethoxybenzoic acid (36 mg,
0.17 mmol) following general procedure 2. 1H NMR (400 MHz,
160.74, 139.92, 132.98, 130.42, 130.00, 128.70, 125.46, 122.91,þ119.24,
51.86, 23.88, 23.07, 22.01. Mp: 257e258 ꢂC. HRMS: [MþH] calcd
[C17H21N3O4S2þH]þ 396.1052, found 396.1053. HPLC: gradient A,
98.7% purity, 6.8 min.
DMSO‑d6)
d
10.51 (s, 1H), 8.47 (s, 1H), 8.08 (s, 4H), 7.65 (d, J ¼ 7.4 Hz,
1H), 7.61 (d, J ¼ 8.0 Hz, 1H), 7.32 (s, 2H), 3.87 (s, 6H), 3.73 (s, 3H),
3.65e3.58 (m, 1H), 1.65e1.43 (m, 3H), 0.84 (d, J ¼ 6.0 Hz, 6H). 13
C
5.1.37. Benzyl (3-(N-L-leucylsulfamoyl)phenyl)carbamate (82)
Compound 82 (50 mg, 61.0% yield) was prepared from 25
(100 mg, 0.18 mmol) in the presence of HCl gas. 1H NMR (400 MHz,
NMR (151 MHz, DMSO‑d6)
d 165.62, 153.15, 141.09, 140.13, 129.95,
129.72, 122.96, 119.57, 105.91, 60.63, 56.63, 52.04, 23.88, 23.16,
21.83. Mp: 242e244 ꢂC. HRMS: [MþH]þ calcd [C22H29N3O7SþH]þ
480.1804, found 480.1803. HPLC: gradient A, 99.5% purity, 7.2 min.
DMSO‑d6)
d
10.25 (s, 1H), 8.34 (s, 3H), 8.25 (s, 1H), 7.70 (d, J ¼ 7.7 Hz,
1H), 7.59e7.52 (m, 2H), 7.47e7.32 (m, 5H), 5.19 (s, 2H), 3.83 (s, 1H),
1.68e1.46 (m, 3H), 0.83 (d, J ¼ 6.1 Hz, 6H). 13C NMR (101 MHz,
5.1.33. N-(3-(N-L-Leucylsulfamoyl)phenyl)-4-phenoxybenzamide
(78)
Compound 78 (18.7 mg, 23.5% yield) was prepared from 26
(59 mg, 0.15 mmol) and 4-phenoxybenzoic acid (36 mg, 0.17 mmol)
following general procedure 2. 1H NMR (400 MHz, DMSO‑d6)
DMSO‑d6) d 153.80, 140.28, 136.84, 130.08, 128.96, 128.62, 128.60,
121.95, 117.06, 66.52, 51.87, 23.85, 23.06, 22.00. Mp: 252e253 ꢂC.
HRMS: [MþH]þ calcd [C20H25N3O5SþH]þ 420.1593, found
420.1587. HPLC: gradient A, 98.0% purity, 8.2 min.
d
10.62 (s, 1H), 8.57 (s, 1H), 8.24 (s, 2H), 8.11e8.03 (m, 3H), 7.67 (d,
5.1.38. N-(3-(N-L-Leucylsulfamoyl)phenyl)-(1,10-biphenyl)-3-
carboxamide (83)
Compound 83 (52 mg, 55.0% yield) was prepared from 26
(73 mg, 0.19 mmol) and (1,10-biphenyl)-3-carboxylic acid (41 mg,
0.21 mmol) following general procedure 2. 1H NMR (400 MHz,
J ¼ 8.0 Hz, 1H), 7.61 (t, J ¼ 8.0 Hz, 1H), 7.48 (t, J ¼ 8.0 Hz, 2H), 7.25 (t,
J ¼ 7.4 Hz, 1H), 7.12 (dd, J ¼ 8.2, 5.0 Hz, 4H), 3.82 (s, 1H), 1.67e1.49
(m, 3H), 0.85 (d, J ¼ 4.8 Hz, 6H). 13C NMR (101 MHz, DMSO‑d6)
d
169.64, 165.51, 160.60, 155.89, 140.34, 130.78, 130.62, 129.88,
129.22, 125.43, 124.97, 122.90, 120.13, 119.29, 117.85, 51.93, 23.88,
23.10, 21.99. Mp: 268e269 ꢂC. HRMS: [MþH]þ calcd
[C25H27N3O5SþH]þ 482.1750, found 482.1752. HPLC: gradient A,
99.1% purity, 9.2 min.
DMSO‑d6)
d
10.81 (s, 1H), 8.59 (s, 1H), 8.29 (s, 4H), 8.14 (d, J ¼ 8.1 Hz,
1H), 8.00 (d, J ¼ 7.9 Hz, 1H), 7.92 (d, J ¼ 7.9 Hz, 1H), 7.83e7.77 (m,
2H), 7.72e7.67 (m, 1H), 7.67e7.59 (m, 2H), 7.53 (t, J ¼ 7.6 Hz, 2H),
7.44 (t, J ¼ 7.3 Hz, 1H), 3.85 (s, 1H), 1.68e1.46 (m, 3H), 0.86 (d,
J ¼ 5.7 Hz, 6H). 13C NMR (101 MHz, DMSO‑d6)
d 169.60, 166.23,
5.1.34. N-(3-(N-L-Leucylsulfamoyl)phenyl)-3-phenoxybenzamide
(79)
Compound 79 (15.1 mg, 19.5% yield) was prepared from 26
(59 mg, 0.15 mmol) and 3-phenoxybenzoic acid (36 mg, 0.17 mmol)
following general procedure 2. 1H NMR (400 MHz, DMSO‑d6)
140.83,140.28,139.90,135.38,130.63,129.84,129.52,128.38,127.46,
126.46, 125.63, 123.06, 119.þ40, 51.84, 23.89, 23.10, 22.03. Mp:
258e259 ꢂC. HRMS: [MþH] calcd [C25H27N3O4SþH]þ 466.1801,
found 466.1810. HPLC: gradient A, 99.8% purity, 10.8 min.
d
10.69 (s, 1H), 8.55 (s, 1H), 8.24 (s, 2H), 8.06 (d, J ¼ 8.0 Hz, 1H), 7.81
5.1.39. N-(3-(N-L-Leucylsulfamoyl)phenyl)-(1,10-biphenyl)-4-
carboxamide (84)
Compound 84 (50 mg, 53.0% yield) was prepared from 26
(73 mg, 0.19 mmol) and (1,10-biphenyl)-4-carboxylic acid (41 mg,
0.21 mmol) following general procedure 2. 1H NMR (400 MHz,
(d, J ¼ 8.2 Hz, 1H), 7.68 (d, J ¼ 8.0 Hz, 1H), 7.65e7.63 (m, 1H),
7.62e7.59 (m,1H), 7.57 (d, J ¼ 7.9 Hz,1H), 7.45 (t, J ¼ 7.8 Hz, 2H), 7.26
(dd, J ¼ 8.2, 2.4 Hz, 1H), 7.21 (t, J ¼ 7.3 Hz, 1H), 7.09 (d, J ¼ 8.4 Hz,
2H), 3.81 (s, 1H), 1.68e1.45 (m, 3H), 0.84 (dd, J ¼ 5.9, 3.9 Hz, 6H). 13
C
NMR (101 MHz, DMSO‑d6)
d
165.46, 157.32, 156.69, 140.05, 136.58,
DMSO‑d6)
d
10.73 (s, 1H), 8.62 (s, 1H), 8.25 (s, 3H), 8.12 (t, J ¼ 7.2 Hz,
130.77, 130.70, 129.92, 124.41, 123.20, 123.16, 122.44, 119.41, 119.37,
118.12, 52.00, 23.87, 23.12, 21.88. Mp: 273e275 ꢂC. HRMS: [MþH]þ
calcd [C25H27N3O5SþH]þ 482.1750, found 482.1751. HPLC: gradient
A, 99.8% purity, 9.1 min.
3H), 7.87 (d, J ¼ 8.5 Hz, 2H), 7.81e7.76 (m, 2H), 7.69 (d, J ¼ 8.0 Hz,
1H), 7.63 (t, J ¼ 7.9 Hz, 1H), 7.53 (t, J ¼ 7.5 Hz, 2H), 7.45 (t, J ¼ 7.3 Hz,
1H), 3.83 (s, 1H), 1.67e1.52 (m, 3H), 0.86 (d, J ¼ 5.4 Hz, 6H). 13C NMR
(101 MHz, DMSO‑d6) d 169.56, 165.95, 143.94, 140.35, 139.47, 133.41,
129.97, 129.57, 129.03, 128.72, 127.42, 127.13, 125.60, 123.03,þ119.32,
51.82, 23.88, 23.09, 22.04. Mp: 279e280 ꢂC. HRMS: [MþH] calcd
[C25H27N3O4SþH]þ 466.1801, found 466.1799. HPLC: gradient A,
99.3% purity, 10.8 min.
5.1.35. N-(3-(N-L-Leucylsulfamoyl)phenyl)furan-2-carboxamide
(80)
Compound 80 (18.9 mg, 23.9% yield) was prepared from 26
(73 mg, 0.19 mmol) and furan-2-carboxylic acid (24 mg, 0.21 mmol)
following general procedure 2. 1H NMR (400 MHz, DMSO‑d6)
5.1.40. N-(3-(N-L-Leucylsulfamoyl)phenyl)-30-methoxy-(1,10-
biphenyl)-3-carboxamide (85)
d
10.64 (s, 1H), 8.52 (s, 1H), 8.25 (s, 3H), 8.07 (d, J ¼ 7.9 Hz, 1H), 7.98
(d, J ¼ 1.0 Hz, 1H), 7.67 (d, J ¼ 8.0 Hz, 1H), 7.60 (t, J ¼ 7.9 Hz, 1H), 7.47
Compound 85 (28 mg, 25.2% yield) was prepared from 26
8