Journal of Medicinal Chemistry
Page 18 of 21
(8). 1H NMR (400 MHz, Acetone-d6) δ 7.76 – 7.58 (m, 5H), 7.52 4-(N-(3,5-bis(trifluoromethyl)benzyl)acetamido)-N-
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– 7.43 (m, 1H), 7.37 (s, 1H), 7.22 – 7.20, 7.12 (m, 4H), 5.24 (s, hydroxybenzamide (14). H NMR (700 MHz, Methanol-d4) δ
2H), 1.28 (s, 18H). 13C NMR (101 MHz, Acetone-d6) δ 205.3, 7.84 (s, 1H), 7.84 – 7.77 (m, 4H), 7.26 (d, J = 8.5 Hz, 2H), 5.09
168.3, 150.7, 145.9, 137.5, 136.4, 132.3, 130.2, 129.9, 129.5, (s, 2H), 1.94 (s, 3H). 13C NMR (176 MHz, Methanol-d4) δ 174.2,
129.0, 127.9, 127.7, 126.3, 125.4, 122.4, 121.0, 53.5, 34.4, 30.8. 168.1, 147.4, 143.1 134.9, 134.1, 131.4, 131.1, 130.6, 125.9,
19F NMR (376 MHz, Acetone-d6) δ -63.35 (s, 3F). HRMS (ESI+) 123.6, 54.1, 23.8. 19F NMR (658 MHz, Methanol-d4) δ -64.44 (s,
m/z calcd for [C30H34F3N2O3]+: 527.2516, found: 527.2518. 6F). HRMS (ESI+) m/z calcd for [C18H15F6N2O3]+: 421.0979,
HPLC tR = 28.483 min (>99% purity).
found: 421.0978. HPLC tR = 20.187 min (98.6% purity).
N-(4-(hydroxycarbamoyl)phenyl)-3-(trifluoromethyl)-N-(3-
N-(cyclopropylmethyl)-N-(4-(hydroxycarbamoyl)phenyl)-3-
1
(trifluoromethyl)benzyl)benzamide (9). H NMR (700 MHz, (trifluoromethyl)benzamide (15). 1H NMR (700 MHz,
Methanol-d4) δ 7.66 (s, 1H), 7.60 – 7.56 (m, 6H), 7.54 (d, J = 7.7 Methanol-d4) δ 7.67 (d, J = 8.5 Hz, 2H), 7.61 (s, 1H), 7.56 (d, J =
Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.14 7.9 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H),
(d, J = 8.6 Hz, 2H), 5.28 (s, 2H).13C NMR (176 MHz, Methanol- 7.29 (d, J = 8.5 Hz, 2H), 3.84 (d, J = 7.2 Hz, 2H), 1.11 – 1.04 (m,
d4) δ 172.3, 168.0, 147.7, 140.6, 139.0, 134.6, 133.7, 132.9, 1H), 0.48 – 0.41 (m, 2H), 0.18 – 0.12 (m, 2H). 13C NMR (176
131.8, 131.4, 130.6, 130.5, 129.1, 129.0, 127.9, 127.6, 127.0, MHz, Methanol-d4) δ 172.1, 168.2, 148.5, 139.6, 134.4, 133.6,
126.8, 126.0, 125.5, 55.3. 19F NMR (658 MHz, Methanol-d4) δ - 132.7, 131.3, 131.0, 130.5, 128.7, 127.7, 126.3, 57.1, 11.9, 5.5.
64.24 (s, 3F), -64.50 (s, 3F). HRMS (ESI+) m/z calcd for 19F NMR (658 MHz, Methanol-d4) δ -64.38 (s, 3F). HRMS
[C23H17F6N2O3]+: 483.1147, found: 483.1144. HPLC tR = 23.546 (ESI+) m/z calcd for [C19H18F3N2O3]+: 379.1262, found:
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min (>99% purity).
379.1259. HPLC tR = 21.253 min (>99% purity).
N-benzyl-N-(4-(hydroxycarbamoyl)phenyl)-3-
N-(4-(hydroxycarbamoyl)phenyl)-N-isopropyl-3-
(trifluoromethyl)benzamide (10). 1H NMR (700 MHz, (trifluoromethyl)benzamide (16). 1H NMR (700 MHz,
Methanol-d4) δ 7.66 (s, 1H), 7.60 – 7.50 (m, 4H), 7.36 (t, J = 7.8 Methanol-d4) δ 7.66 (d, J = 8.3 Hz, 2H), 7.57 (s, 1H), 7.50 (t, J =
Hz, 1H), 7.28 (d, J = 7.3 Hz, 2H), 7.24 (t, J = 7.3 Hz, 2H), 7.20 7.7 Hz, 2H), 7.36 (t, J = 7.9 Hz, 1H), 7.27 (d, J = 8.3 Hz, 2H),
(t, J = 7.3 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 5.18 (s, 2H). 13C 4.99 (br, 1H), 1.23 (d, J = 6.9 Hz, 6H). 13C NMR (176 MHz,
NMR (176 MHz, Methanol-d4) δ 172.2, 168.1, 147.9, 139.3, Methanol-d4) δ 172.3, 168.1, 144.5, 140.5, 134.4, 133.9, 133.4,
139.2, 134.6, 133.5, 132.7, 131.4, 130.9, 130.8, 130.7, 130.4, 132.6, 131.2, 130.1, 128.3, 127.2, 126.4, 51.3, 22.4. 19F NMR
130.0, 129.0, 127.9, 126.3, 55.8. 19F NMR (658 MHz, Methanol- (658 MHz, Methanol-d4) δ -64.37 (s, 3F). HRMS (ESI+) m/z
d4)
δ -64.22 (s, 3F). HRMS (ESI+) m/z calcd for calcd for [C18H18F3N2O3]+: 367.1264, found: 367.1263. HPLC tR
[C22H18F3N2O3]+: 415.1273, found: 415.1275. HPLC tR = 22.033 = 20.680 min (>99% purity).
min (>99% purity).
3-(tert-butyl)-N-(cyclopropylmethyl)-N-(4-
(hydroxycarbamoyl)phenyl)benzamide (MMH371). H NMR
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N-(4-(hydroxycarbamoyl)phenyl)-3-
(trifluoromethyl)benzamide (11). 1H NMR (700 MHz, (700 MHz, Methanol-d4) δ 7.64 (d, J = 8.6 Hz, 2H), 7.30 (dt, J =
Methanol-d4) δ 8.24 (s, 1H), 8.19 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 7.6, 1.7 Hz, 1H), 7.23 (d, J = 8.6 Hz, 2H), 7.22 – 7.19 (m, 2H),
7.7 Hz, 1H), 7.84 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 8.7 Hz, 2H), 7.17 (t, J = 7.6 Hz, 1H), 3.84 (d, J = 7.1 Hz, 2H), 1.11 (s, 9H),
7.71 (t, J = 7.8 Hz, 1H). 13C NMR (176 MHz, Methanol-d4) δ 1.09 – 1.05 (m, 1H), 0.46 – 0.42 (m, 2H), 0.14 (q, J = 5.2 Hz, 2H).
168.9, 168.4, 144.3, 138.3, 133.6, 133.3, 131.9, 130.7, 130.4, 13C NMR (176 MHz, Methanol-d4) δ 174.3, 168.1, 153.2, 149.3,
130.2, 126.9, 126.6, 122.8. 19F NMR (658 MHz, Methanol-d4) δ 137.9, 133.1, 130.8, 130.28, 130.27, 129.2, 128.3, 128.2, 57.0,
-64.22 (s, 3F). HRMS (ESI+) m/z calcd for [C15H12F3N2O3]+: 36.7, 32.7, 12.0, 5.4. HRMS (ESI+) m/z calcd for [C22H27N2O3]+:
325.0795, found: 325.0794. HPLC tR = 10.522 min (>99% 367.1943, found: 367.2016. HPLC tR = 27.958 min (>99%
purity).
purity).
N-ethyl-N-(4-(hydroxycarbamoyl)phenyl)-2-
3,5-di-tert-butyl-N-(cyclopropylmethyl)-N-(4-
(trifluoromethyl)benzamide (12). 1H NMR (700 MHz, (hydroxycarbamoyl)phenyl)benzamide (17). 1H NMR (700
Methanol-d4) δ 7.61 (d, J = 8.47 Hz, 2H), 7.59 (d, J = 7.7 Hz, 1H), MHz, Methanol-d4) δ 7.66 (d, J = 8.3 Hz, 2H), 7.33 (s, 1H), 7.22
7.40 – 7.33 (m, 2H), 7.26 – 7.24 (m, 3H), 3.99 (br, 2H), 1.22 (t, J (d, J = 8.1 Hz, 2H), 7.14 (s, 2H), 3.85 (d, J = 7.2 Hz, 2H), 1.15 (s,
= 7.2 Hz, 3H). 13C NMR (176 MHz, Methanol-d4) δ 171.0, 168.1, 18H), 0.43 (q, J = 7.9 Hz, 2H), 0.14 (q, J = 5.2 Hz, 2H). 13C NMR
147.1, 137.1, 134.1, 134.0, 131.9, 131.4, 130.9, 130.5, 129.7, (176 MHz, Methanol-d4) δ 174.6, 168.0, 153.0, 149.6, 137.3,
129.0, 126.6, 47.1, 14.1. 19F NMR (658 MHz, Methanol-d4) δ - 132.9, 130.7, 130.3, 126.1, 125.8, 57.0, 36.9, 32.9, 12.0, 5.5.
59.94 (s, 3F). HRMS (ESI+) m/z calcd for [C17H16F3N2O3]+: HRMS (ESI+) m/z calcd for [C26H35N2O3]+: 423.2642, found:
353.1108, found: 353.1107. HPLC tR = 9.442 min (>99% purity). 423.2636. HPLC tR = 34.486 min (>99% purity).
N-hydroxy-4-(N-(3-
3,5-di-tert-butyl-N-(cyclopropylmethyl)-N-(4-
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(trifluoromethyl)benzyl)acetamido)benzamide (13). H NMR (hydroxycarbamoyl)phenyl)benzamide (18). 1H NMR (700
(700 MHz, Methanol-d4) δ 7.76 (d, J = 8.4 Hz, 2H), 7.53 (d, J = MHz, Methanol-d4) δ 7.85-7.80 (m, 2H), 7.79 – 7.73 (m, 4H),
7.2 Hz, 1H), 7.49 (s, 1H), 7.48 – 7.43 (m, 2H), 7.23 (d, J = 8.4 7.69 – 7.65 (m, 1H), 1.37 (s, 18H). 13C NMR (176 MHz,
Hz, 2H), 5.01 (s, 2H), 1.92 (s, 3H). 13C NMR (176 MHz, Methanol-d4) δ 171.3, 169.0, 153.8, 144.6, 136.8, 130.1, 130.1,
Methanol-d4) δ 174.0, 168.2, 147.6, 141.0, 134.7, 134.6, 133.1, 128.6, 124.2, 122.9, 37.2, 33.0. HRMS (ESI+) m/z calcd for
131.7, 130.9, 130.7, 127.5, 126.6, 126.0, 54.4, 23.9. 19F NMR [C22H29N2O3]+: 369.2173, found: 369.2172. HPLC tR = 35.032
(658 MHz, Methanol-d4) δ -64.21 (s, 3F). HRMS (ESI+) m/z min (>99% purity).
calcd for [C17H16F3N2O3]+: 353.1108, found: 353.1108. HPLC tR
= 18.616 min (98.3% purity).
N-(4-(hydroxycarbamoyl)phenyl)-N-isopropyl-3,5-
bis(trifluoromethyl)benzamide (MMH409). 1H NMR (700
MHz, Methanol-d4) δ 7.85 (s, 2H), 7.80 (s, 1H), 7.70 (d, J = 8.2
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