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Title: Design, Synthesis, and Biological Evaluation of AV6 Derivatives as Novel Dual Reactivator of Latent HIV-1
Authors: Mingtao Ao, a# Zhenrui Pan,a#, Yuqing Qian,a#, Bowen Tang,a Zeming Feng,a Hua Fang,b Zhen Wu,a Jinwei
Chen,b* Yuhua Xuea* and Meijuan Fanga*
Supporting Information
1. Figure S1. Overlay of co-crystal SAHA and re-docked SAHA bound in the
HDAC2 (PDB entry 4LXZ) ligand binding pocket
2. Figure S2. Overlay of 12c and 12d bound in the HDAC2 (PDB entry 4LXZ) ligand
binding pocket
3. Spectra data of compounds 7b~7B, 9b~9e, 10a~10b, 11b~11d and 12a~12b
4. The 1H and 13C NMR spectra of compounds 2, 3, 7a~7B, 9a~9e, 10a~10d,
11a~11d and 12a~12d
Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2018
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Figure S1. Overlay of co-crystal SAHA (blue carbon in stick representation) and re-docked SAHA (yellow carbon
in stick representation) bound in the HDAC2 (PDB entry 4LXZ) ligand binding pocket
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Figure S2. Overlay of 12c (brown carbon in stick representation) and 12d (dark green carbon in stick representation)
bound in the HDAC2 (PDB entry 4LXZ) ligand binding pocket
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Spectra data of compounds 7b~7B
N-(3-bromo-4-chlorophenyl)-6-methoxy-2-methylquinolin-4-amine (7b). White
solid; Yield: 35.9 %; HPLC purity: 99.3 % (tR = 22.27 min); mp: 251-252 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 7.81-7.85 (m, 2H, H-5 and H-8), 7.77 (d, J = 2.4 Hz, 1H, Ph-
H), 7.66 (d, J = 8.6 Hz, 1H, Ph-H), 7.46 (dd, J = 2.4, 8.6 Hz, 1H, Ph-H), 7.43 (dd, J =
2.4, 9.2 Hz, 1H, H-7), 6.92 (s, 1H, H-3), 3.94 (s, 3H, OCH3), 2.52 (s, 3H, CH3); 13C
NMR (150 MHz, DMSO-d6): δ 157.3 (C-2), 155.0 (C-6), 151.8 (C-4), 149.6 (C-9),
140.4 (C-1’), 131.6 (C-8), 128.7 (Ph-C), 128.2 (Ph-C), 126.4 (C-7), 124.0 (Ph-C), 123.5
(Ph-C), 122.5 (Ph-C), 118.9 (C-10), 102.7 (C-3), 102.3 (C-5), 56.5 (OCH3), 22.8 (CH3).
ESI-HRMS (+): m/z [M+H]+ calculated for C17H15BrClN2O+, 377.0051, found,
377.0049.
N-(4-chloro-3-fluorophenyl)-6-methoxy-2-methylquinolin-4-amine (7c). White
solid; Yield: 41.1 %; HPLC purity: 99.4 % (tR = 20.93 min); mp: 296-297 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 10.70 (br. s., 1H, NH), 8.16 (s, 1H, H-5), 8.00 (d, J = 9.2 Hz,
1H, H-8), 7.75 (t, J = 8.5 Hz, 1H, Ph-H), 7.60-7.66 (m, 2H), 7.39 (d, J = 7.5 Hz, 1H,
Ph-H), 6.92 (s, 1H, H-3), 3.98 (s, 3H, OCH3), 2.62 (s, 3H, CH3); 13C NMR (150 MHz,
DMSO-d6): δ 158.8 (d, J = 245.4 Hz, 1C, C-F), 158.1 (C-2), 153.4 (C-6), 152.9 (C-4),
139.0 (d, J = 9.9 Hz, 1C, C-1’), 134.6 (C-9), 131.9 (C-8), 125.3 (C-7), 122.7 (Ph-C),
122.3 (Ph-C), 118.2 (C-10), 117.4 (d, J = 16.5 Hz, 1C, C-4’), 114.1 (d, J = 23.1 Hz, 1C,
C-2’), 103.4 (C-3), 101.5 (C-5), 56.9 (OCH3), 20.3 (CH3). ESI-HRMS (+): m/z [M+H]+
calculated for C17H15ClFN2O+, 317.0851, found, 317.0850.
N-(4-chloro-3-methylphenyl)-6-methoxy-2-methylquinolin-4-amine (7d). White
solid; Yield: 40.1 %; HPLC purity: 99.2 % (tR = 21.97 min); mp: 282-283 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 10.46 (br. s., 1H, NH), 8.14 (d, J = 2.2 Hz, 1H, H-5), 7.98 (d,
J = 9.2 Hz, 1H, H-8), 7.58-7.60 (m, 1H, H-7), 7.57 (d, J = 8.4 Hz, 1H, Ph-H), 7.46 (d,
J = 2.4 Hz, 1H, Ph-H), 7.33 (dd, J = 2.4, 8.4 Hz, 1H, Ph-H), 6.72 (s, 1H, H-3), 3.97 (s,
3H, OCH3), 2.58 (s, 3H, 11-CH3), 2.39 (s, 3H, 13-CH3); 13C NMR (150 MHz, DMSO-
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d6): δ 158.0 (C-2), 153.3 (C-6), 153.0 (C-4), 137.6 (C-9), 137.2 (C-1’), 135.1 (Ph-C),
131.4 (C-8), 130.6 (Ph-C), 128.1 (Ph-C), 125.0 (C-7), 124.7 (Ph-C), 122.7 (Ph-C),
118.0 (C-10), 103.1 (C-3), 100.8 (C-5), 56.8 (O-CH3), 20.6 (11-CH3), 20.2 (13-CH3).
ESI-HRMS (+): m/z [M+H]+ calculated for C18H18ClN2O+, 313.1102, found, 313.1101.
N-(4-chloro-3-methoxyphenyl)-6-methoxy-2-methylquinolin-4-amine (7e). White
solid; Yield: 35.1 %; HPLC purity: 99.5 % (tR = 20.50 min); mp: 253-255 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 7.76 (d, J = 9.0 Hz, 1H, H-8), 7.73 (d, J = 2.4 Hz, 1H, H-5),
7.44 (d, J = 8.4 Hz, 1H, Ph-H), 7.36 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 7.12 (d, J = 2.4 Hz,
1H, Ph-H), 6.97 (dd, J = 2.2, 8.4 Hz, 1H, Ph-H), 6.92 (s, 1H, H-3), 3.93 (s, 3H, 4’-
OCH3), 3.87 (s, 3H, 6-OCH3), 2.47 (s, 3H, 11-CH3). 13C NMR (150 MHz, DMSO-d6):
δ 156.7 (C-2), 156.0 (Ph-C), 155.5 (C-6), 147.8 (C-4), 143.1 (C-9), 141.3 (C-1’), 130.7
(C-8), 129.1 (C-7), 122.0 (Ph-C), 119.3 (C-10), 115.8 (Ph-C), 115.3 (Ph-C), 107.6 (Ph-
C), 103.0 (C-3), 101.7 (C-5), 56.5 (6-OCH3), 56.2 (4’-OCH3), 24.5 (C-11). ESI-HRMS
(+): m/z [M+H]+ calculated for C18H18ClN2O2+, 329.1051, found, 329.1047.
N-(3,4-dichlorophenyl)-6-ethoxy-2-methylquinolin-4-amine (7f). White solid;
Yield: 33.4 %; HPLC purity: 99.1 % (tR = 23.02 min); mp: 221-223 ºC. 1H NMR (600
MHz, DMSO-d6): δ 7.75 (d, J = 8.8 Hz, 1H, H-8), 7.59-7.66 (m, 2H), 7.55 (s, 1H, Ph-
H), 7.32-7.40 (m, 2H), 6.96 (s, 1H, H-3), 4.18 (d, J = 6.6 Hz, 2H, OCH2CH3), 2.47 (s,
3H, 11-CH3), 1.41 (t, J = 6.3 Hz, 3H, OCH2CH3); 13C NMR (150 MHz, DMSO-d6): δ
156.1 (C-2), 156.0 (C-6), 146.6 (C-4), 143.5 (C-9), 141.9 (C-1’), 132.0 (Ph-C), 131.6
(C-8), 129.6 (Ph-C), 124.7 (C-7), 123.2 (Ph-C), 122.1 (Ph-C), 121.6 (Ph-C), 119.6 (C-
10), 103.8 (C-3), 102.3 (C-5), 64.1 (OCH2CH3), 24.7 (C-11), 15.1 (OCH2CH3). ESI-
HRMS (+): m/z [M+H]+ calculated for C18H17Cl2N2O+, 347.0712, found, 347.0711.
N-(3-bromo-4-chlorophenyl)-6-ethoxy-2-methylquinolin-4-amine (7g). White
solid; Yield: 50.2 %; HPLC purity: 98.5 % (tR = 23.28 min); mp: 243-245 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.91 (br. s., 1H, NH), 7.74 (d, J = 9.2 Hz, 1H, H-8), 7.67 (s,
1H, H-5), 7.57-7.63 (m, 2H, Ph-H), 7.40 (d, J = 7.3 Hz, 1H, Ph-H), 7.33 (d, J = 7.7 Hz,
1H, H-7), 6.95 (s, 1H, H-3), 4.17 (q, J = 6.7 Hz, 2H, , OCH2CH3), 2.47 (s, 3H, 11-CH3),
1.41 (t, J = 6.8 Hz, 3H, OCH2CH3); 13C NMR (150 MHz, DMSO-d6): δ 156.3 (C-2),
155.9 (C-6), 146.3 (C-4), 144.1 (C-9), 142.0 (C-1’), 131.3 (C-8), 129.9 (Ph-C), 126.5
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(Ph-C), 126.2 (C-7), 122.3 (Ph-C), 122.0 (Ph-C), 121.9 (Ph-C), 119.7 (C-10), 103.9 (C-
3), 102.2 (C-5), 64.1 (OCH2CH3), 24.9 (C-11), 15.1 (OCH2CH3). ESI-HRMS (+): m/z
[M+H]+ calculated for C18H17BrCl2N2O+, 391.0207, found, 391.0207.
N-(4-chloro-3-fluorophenyl)-6-ethoxy-2-methylquinolin-4-amine (7h). White solid;
Yield: 79.4 %; HPLC purity: 98.5 % (tR = 21.98 min); mp: 247-248 ºC. 1H NMR (600
MHz, DMSO-d6): δ 7.76 (d, J = 9.2 Hz, 1H, H-8), 7.67 (d, J = 2.6 Hz, 1H, H-5), 7.58
(t, J = 8.6 Hz, 1H, Ph-H), 7.33-7.41 (m, 2H), 7.23 (dd, J = 2.0, 8.6 Hz, 1H, Ph-H), 6.99
(s, 1H, H-3), 4.18 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.49 (s, 3H, 11-CH3), 1.41 (t, J = 7.0
Hz, 3H, OCH2CH3); 13C NMR (150 MHz, DMSO-d6): δ 158.8 (d, J = 245.4 Hz, 1C, C-
F), 156.1 (C-2), 155.9 (C-6), 147.2 (C-4), 142.1 (d, J = 9.9 Hz, 1C, C-1’), 131.5 (C-8),
128.8 (C-7), 122.4 (C-5’), 119.5 (C-10), 119.0 (C-6’), 113.3 (d, J = 17.6 Hz, 1C, C-4’),
110.1 (d, J = 24.2 Hz, 1C, C-2’), 103.8 (C-3), 102.5 (C-5), 64.2 (OCH2CH3), 24.3 (C-
11), 15.1 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for C18H17ClFN2O+,
331.1008, found, 331.1004.
N-(4-chloro-3-methylphenyl)-6-ethoxy-2-methylquinolin-4-amine (7i). White solid;
Yield: 81.8 %; HPLC purity: 98.5 % (tR = 22.85 min); mp: 207-209 ºC. 1H NMR (600
MHz, DMSO-d6): δ 7.91 (s, 1H, H-5), 7.85 (d, J = 9.2 Hz, 1H, H-8), 7.50 (d, J = 8.4
Hz, 1H, Ph-H), 7.45 (d, J = 9.0 Hz, 1H, H-7), 7.40 (d, J = 1.8 Hz, 1H, Ph-H), 7.27 (dd,
J = 2.2, 8.4 Hz, 1H, Ph-H), 6.76 (s, 1H, H-3), 4.21 (q, J = 7.0 Hz, 2H, OCH2CH 3), 2.51
(s, 3H, 11-CH3), 2.37 (s, 3H, 14-CH3), 1.42 (t, J = 7.0 Hz, 3H, OCH2CH3); 13C NMR
(150 MHz, DMSO-d6): δ 156.6 (C-2), 154.5 (C-6), 150.7 (C-4), 138.4 (C-9), 137.3 (Ph-
C), 130.3 (Ph-C), 130.3 (C-8), 129.9 (Ph-C), 126.9 (Ph-C), 125.6 (C-7), 123.8 (Ph-C),
123.5 (Ph-C), 118.5 (C-10), 103.0 (C-3), 101.5 (C-5), 64.5 (OCH2CH3), 22.4 (C-11),
20.2 (14-CH3), 15.0 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for
C19H20ClN2O+, 327.1259, found, 327.1249.
N-(4-chloro-3-methoxyphenyl)-6-ethoxy-2-methylquinolin-4-amine (7j). White
solid; Yield: 52.2 %; HPLC purity: 98.5 % (tR = 21.77 min); mp: 206-208 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.72 (s, 1H, NH), 7.71 (d, J = 9.2 Hz, 1H, H-8), 7.64 (d, J =
2.4 Hz, 1H, H-5), 7.41 (d, J = 8.4 Hz, 1H, Ph-H), 7.30 (dd, J = 2.5, 9.1 Hz, 1H, H-7),
7.08 (d, J = 1.5 Hz, 1H, Ph-H), 6.92-6.96 (m, 2H), 4.18 (q, J = 7.0 Hz, 2H, OCH2CH3),
3.86 (s, 3H, 14-CH3), 2.44 (s, 3H, 11-CH3), 1.41 (t, J = 6.9 Hz, 3H, OCH2CH3); 13C
NMR (150 MHz, DMSO-d6): δ 156.5 (C-2), 155.7 (C-3’), 155.5 (C-6), 146.7 (C-4),
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144.7 (C-9), 141.9 (C-1’), 130.6 (Ph-C), 130.4 (C-8), 121.5 (C-7), 119.5 (C-10), 115.1
(Ph-C), 114.7 (Ph-C), 107.0 (Ph-C), 103.3 (C-3), 102.1 (C-5), 64.0 (OCH2CH3), 56.5
(14-CH3), 25.3 (C-11), 15.1 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for
C19H20ClN2O2+, 343.1208, found, 343.1203.
N-(4-chloro-3-nitrophenyl)-6-ethoxy-2-methylquinolin-4-amine (7k). White solid;
Yield: 85.7 %; HPLC purity: 98.7 % (tR = 21.13 min); mp: 264-266 ºC. 1H NMR (600
MHz, DMSO-d6): δ 10.80 (br. s., 1H, NH), 8.22 (d, J = 2.6 Hz, 1H, H-5), 8.14 (d, J =
2.4 Hz, 1H, Ph-H), 8.01 (d, J = 9.2 Hz, 1H, H-8), 7.93 (d, J = 8.8 Hz, 1H, Ph-H), 7.86
(dd, J = 2.6, 8.6 Hz, 1H, Ph-H), 7.65 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 7.02 (s, 1H, H-3),
4.27 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.63 (s, 3H, 11-CH3), 1.43 (t, J = 7.0 Hz, 3H,
OCH2CH3); 13C NMR (150 MHz, DMSO-d6): δ 160.0 (C-NO2), 157.5 (C-2), 153.4 (C-
6), 152.8 (C-4), 148.5 (C-9), 138.5 (C-1’), 134.2 (Ph-C), 133.3 (Ph-C), 130.5 (C-8),
125.8 (C-7), 122.4 (Ph-C), 122.2 (Ph-C), 118.3 (C-10), 103.9 (C-3), 101.7 (C-5), 64.9
(OCH2CH3), 20.1 (C-11), 14.9 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for
C18H17ClN3O3+, 358.0953, found, 358.0949.
2-chloro-5-((6-methoxy-2-methylquinolin-4-yl)amino)benzoic acid (7l). White
solid; Yield: 45.3 %; HPLC purity: 91.9 % (tR = 20.88 min); mp: 216-217 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 7.72 (d, J = 2.9 Hz, 1H, H-5), 7.24 (d, J = 8.8 Hz, 1H, H-8),
6.91 (d, J = 8.4 Hz, 1H, Ph-H), 6.88 (d, J = 2.8 Hz, 1H, Ph-H), 6.86 (dd, J = 3.0, 8.9
Hz, 1H, H-7), 6.65 (dd, J = 2.8, 8.4 Hz, 1H, Ph-H), 5.97 (s, 1H, H-3), 4.03 (q, J = 6.9
Hz, 2H, OCH2CH3), 2.04 (s, 3H, 11-CH3), 1.34 (t, J = 6.9 Hz, 3H, OCH2CH3); 13C
NMR (150 MHz, DMSO-d6): δ 171.8 (C=O), 157.1 (C-2), 155.2 (C-6), 155.0 (C-4),
152.7 (C-9), 145.4 (C-1’), 143.5 (Ph-C), 129.0 (C-8), 127.5 (Ph-C), 125.3 (C-7), 122.6
(Ph-C), 122.0 (Ph-C), 118.6 (C-10), 117.1 (Ph-C), 105.0 (C-3), 97.0 (C-5), 63.3
(OCH2CH3), 25.1 (C-11), 15.4 (OCH2CH3). ESI-HRMS (-): m/z [M-H]- calculated for
C19H16ClN2O3-, 355.8055, found, 355.8055.
Butyl 2-chloro-5-((6-ethoxy-2-methylquinolin-4-yl)amino)benzoate (7m). White
solid; Yield: 41.0 %; HPLC purity: 96.1 % (tR = 24.55 min); mp: 151-153 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.87 (br. s., 1H, NH), 7.74 (d, J = 9.0 Hz, 1H, H-8), 7.72 (d,
J = 2.2 Hz, 1H, H-5), 7.61 (d, J = 2.8 Hz, 1H, Ph-H), 7.55-7.58 (m, 1H, Ph-H), 7.52-
7.55 (m, 1H, Ph-H), 7.32 (dd, J = 2.7, 9.1 Hz, 1H, H-7), 6.95 (s, 1H, H-3), 4.30 (t, J =
6.4 Hz, 2H, 14-CH2), 4.17 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.45 (s, 3H, 11-CH3), 1.65-
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1.72 (m, 2H), 1.38-1.46 (m, 5H), 0.92 (t, J = 7.4 Hz, 3H, 17-CH3); 13C NMR (150 MHz,
DMSO-d6): δ 165.3 (C=O), 156.5 (C-2), 155.8 (C-6), 146.0 (C-4), 144.8 (C-9), 141.0
(C-1’), 132.1 (Ph-C), 131.3 (C-8), 130.5 (Ph-C), 125.5 (Ph-C), 125.0 (C-7), 123.4 (Ph-
C), 121.7 (Ph-C), 119.7 (C-10), 103.7 (C-3), 102.1 (C-5), 65.5 (C-14), 64.0
(OCH2CH3), 30.6 (C-15), 25.2 (C-11), 19.2 (C-16), 15.1 (OCH2CH3), 14.0 (C-17). ESI-
HRMS (+): m/z [M+H]+ calculated for C21H26ClN2O3+, 413.1626, found, 413.1626.
2-chloro-5-((6-ethoxy-2-methylquinolin-4-yl)amino)-N-hydroxybenzamide (7n).
White solid; Yield: 45.3 %; HPLC purity: 90.9 % (tR = 16.91 min); mp: 166-167 ºC. 1H
NMR (600 MHz, DMSO-d6): δ 11.05 (br. s., 1H, CONH-OH), 9.30 (br. s., 1H, CONH-
OH), 8.87 (br. s., 1H, NH), 7.74 (d, J = 9.0 Hz, 1H, H-8), 7.63 (d, J = 2.6 Hz, 1H, H-
5), 7.51 (d, J = 8.6 Hz, 1H, Ph-H), 7.43 (dd, J = 2.6, 8.6 Hz, 1H, Ph-H), 7.33 (dd, J =
2.6, 9.2 Hz, 1H, H-7), 7.31 (d, J = 2.6 Hz, 1H, Ph-H), 6.94 (s, 1H, H-3), 4.17 (q, J = 7.0
Hz, 2H, OCH2CH3), 2.46 (s, 3H, 11-CH3), 1.41 (t, J = 7.0 Hz, 3H, OCH2CH3); 13C
NMR (150 MHz, DMSO-d6): δ 163.5 (C=O), 156.3 (C-2), 155.8 (C-6), 146.6 (C-4),
144.2 (C-9), 140.5 (C-1’), 135.7 (Ph-C), 131.1 (C-8), 130.0 (Ph-C), 124.2 (C-7), 123.9
(Ph-C), 122.2 (Ph-C), 121.8 (Ph-C), 119.6 (C-10), 103.2 (C-3), 102.2 (C-5), 64.1
(OCH2CH3), 25.0 (C-11), 15.1 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for
C19H19ClN3O3+, 372.1109, found, 372.1101.
N-(3,4-dichlorophenyl)-6-isopropoxy-2-methylquinolin-4-amine (7o). White solid;
Yield: 58.1 %; HPLC purity: 97.2 % (tR = 23.47 min); mp: 241-243 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.80 (br. s., 1H, NH), 7.74 (d, J = 9.2 Hz, 1H), 7.61 (d, J = 8.8 Hz,
1H, Ph-H), 7.60 (d, J = 2.8 Hz, 1H, H-5), 7.52 (d, J = 2.4 Hz, 1H, Ph-H), 7.34 (dd, J =
2.3, 8.7 Hz, 1H, Ph-H), 7.31 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 6.96 (s, 1H, H-3), 4.77-4.84
(m, 1H, OCH(CH3)2), 2.46 (s, 3H, 11-CH3), 1.34 (s, 3H, OCH(CH3)2), 1.33 (s, 3H,
OCH(CH3)2); 13C NMR (150 MHz, DMSO-d6): δ 156.6 (C-2), 154.6 (C-6), 145.8 (C-
4), 144.6 (C-9), 142.3 (C-1’), 132.0 (Ph-C), 131.5 (C-8), 130.6 (Ph-C), 124.2 (C-7),
122.8 (Ph-C), 122.3 (Ph-C), 121.3 (Ph-C), 119.9 (C-10), 104.2 (C-3), 103.8 (C-5), 70.1
(OCH(CH3)2), 25.2 (C-11), 22.3 (s, 2C, OCH(CH3)2). ESI-HRMS (+): m/z [M+H]+
calculated for C19H19Cl2N2O+, 361.0869, found, 361.0871.
N-(3-bromo-4-chlorophenyl)-6-isopropoxy-2-methylquinolin-4-amine (7p). White
solid; Yield: 68.6 %; HPLC purity: 96.9 % (tR = 23.70 min); mp: 235-237 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.84 (br. s., 1H, NH), 7.74 (d, J = 9.2 Hz, 1H, H-8), 7.65 (d,
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J = 2.4 Hz, 1H, H-5), 7.62 (d, J = 2.6 Hz, 1H, Ph-H), 7.60 (d, J = 8.6 Hz, 1H, Ph-H),
7.39 (dd, J = 2.5, 8.7 Hz, 1H, Ph-H), 7.31 (dd, J = 2.6, 9.0 Hz, 1H, H-7), 6.94 (s, 1H,
H-3), 4.77-4.84 (m, 1H, OCH(CH3)2), 2.46 (s, 3H, 11-CH3), 1.34 (s, 3H, OCH(CH3)2),
1.33 (s, 3H, OCH(CH3)2); 13C NMR (150 MHz, DMSO-d6): δ 156.4 (C-2), 154.7 (C-
6), 146.1 (C-4), 144.2 (C-9), 142.1 (C-1’), 131.3 (C-8), 130.2 (Ph-C), 126.4 (Ph-C),
126.1 (C-7), 122.5 (Ph-C), 122.3 (Ph-C), 121.9 (Ph-C), 119.8 (C-10), 103.9 (C-3),
103.8 (C-5), 70.1 (OCH(CH3)2), 25.1 (C-11), 22.3 (s, 2C, OCH(CH3)2). ESI-HRMS
(+): m/z [M+H]+ calculated for C19H19BrClN2O+, 405.0364, found, 405.0368.
N-(4-chloro-3-fluorophenyl)-6-isopropoxy-2-methylquinolin-4-amine (7q). White
solid; Yield: 77.0 %; HPLC purity: 98.3 % (tR = 22.50 min); mp: 239-241 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.86 (br. s., 1H, NH), 7.74 (d, J = 9.2 Hz, 1H, H-8), 7.62 (d,
J = 2.6 Hz, 1H, H-5), 7.55 (t, J = 8.6 Hz, 1H, Ph-H), 7.29- 7.36 (m, 2H, H-2’ and H-7),
7.20 (dd, J = 2.2, 8.6 Hz, 1H, Ph-H), 6.99 (s, 1H, H-3), 4.77-4.84 (m, 1H, OCH(CH3)2),
2.47 (s, 3H, 11-CH3), 1.34 (s, 3H, OCH(CH3)2), 1.33 (s, 3H, OCH(CH3)2); 13C NMR
(150 MHz, DMSO-d6): δ 158.8 (d, J = 245.4 Hz, 1C, C-F), 156.5 (C-2), 154.7 (C-6),
146.0 (C-4), 144.2 (C-9), 142.7 (C-1’), 131.4 (C-8), 130.2 (C-7), 122.4 (Ph-C), 119.9
(C-10), 118.4 (Ph-C), 112.5 (d, J = 17.6 Hz, 1C, C-4’), 109.6 (d, J = 23.1 Hz, 1C, C-
2’), 104.2 (C-3), 104.0 (C-5), 70.1 (OCH(CH3)2), 25.0 (C-11), 22.3 (s, 2C,
OCH(CH3)2). ESI-HRMS (+): m/z [M+H]+ calculated for C19H19ClFN2O+, 345.1164,
found, 345.1161.
N-(4-chloro-3-methylphenyl)-6-isopropoxy-2-methylquinolin-4-amine (7r). White
solid; Yield: 35.0 %; HPLC purity: 98.3 % (tR = 23.36 min); mp: 222-224 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.78 (br. s., 1H, NH), 7.72 (d, J = 9.2 Hz, 1H, H-8), 7.70 (d,
J = 2.2 Hz, 1H, H-5), 7.43 (d, J = 8.6 Hz, 1H, Ph-H), 7.32 (d, J = 2.2 Hz, 1H, Ph-H),
7.30 (dd, J = 2.5, 9.1 Hz, 1H, H-7), 7.21 (dd, J = 2.4, 8.4 Hz, 1H, Ph-H), 6.80 (s, 1H,
H-3), 4.78-4.86 (m, 1H, OCH(CH3)2), 2.43 (s, 3H, 11-CH3), 2.35 (s, 3H, 15-CH3), 1.34
(s, 3H, OCH(CH3)2), 1.33 (s, 3H, OCH(CH3)2); 13C NMR (150 MHz, DMSO-d6): δ
156.2 (C-2), 154.6 (C-6), 147.3 (C-4), 143.8 (C-9), 140.2 (C-1’), 136.9 (Ph-C), 130.0
(C-8), 129.9 (Ph-C), 127.8 (Ph-C), 125.3 (C-7), 122.4 (Ph-C), 121.8 (Ph-C), 119.4 (C-
10), 103.8 (C-3), 102.5 (C-5), 70.0 (OCH(CH3)2), 24.9 (C-11), 22.3 (s, 2C,
OCH(CH3)2), 20.2 (C-15). ESI-HRMS (+): m/z [M+H]+ calculated for C20H22ClN2O+,
341.1415, found, 341.1412.
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10
N-(4-chloro-3-methoxyphenyl)-6-isopropoxy-2-methylquinolin-4-amine (7s).
White solid; Yield: 67.7 %; HPLC purity: 95.1 % (tR = 22.37 min); mp: 254-255 ºC. 1H
NMR (600 MHz, DMSO-d6): δ 8.70 (s, 1H, NH), 7.72 (d, J = 9.2 Hz, 1H, H-8), 7.66
(d, J = 2.4 Hz, 1H, H-5), 7.41 (d, J = 8.4 Hz, 1H, Ph-H), 7.29 (dd, J = 2.5, 9.2 Hz, 1H,
H-7), 7.08 (d, J = 2.2 Hz, 1H, Ph-H), 6.94 (dd, J = 2.2, 8.4 Hz, 1H, Ph-H), 6.92 (s, 1H,
H-3), 4.77-4.87 (m, 1H, OCH(CH3)2), 3.86 (s, 3H, OCH3), 2.44 (s, 3H, 11-CH3), 1.35
(s, 3H, OCH(CH3)2), 1.34 (s, 3H, OCH(CH3)2); 13C NMR (150 MHz, DMSO-d6): δ
156.6 (C-2), 155.5 (C-3’), 154.5 (C-6), 146.6 (C-4), 144.7 (C-9), 141.9 (C-1’), 130.6
(C-8), 130.1 (C-7), 122.1 (Ph-C), 119.6 (C-10), 115.1 (Ph-C), 114.7 (Ph-C), 107.0 (Ph-
C), 103.9 (C-3), 103.2 (C-5), 70.0 (OCH(CH3)2), 56.5 (OCH3), 25.3 (C-11), 22.3 (s,
2C, OCH(CH3)2). ESI-HRMS (+): m/z [M+H]+ calculated for C20H22ClN2O2+,
357.1364, found, 357.1365.
N-(4-chloro-3-nitrophenyl)-6-isopropoxy-2-methylquinolin-4-amine (7t). White
solid; Yield: 70.6 %; HPLC purity: 98.6 % (tR = 21.95 min); mp: 251-253 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 7.94 (d, J = 2.6 Hz, 1H, Ph-H), 7.77 (d, J = 9.0 Hz, 1H, H-8),
7.72 (d, J = 8.8 Hz, 1H, Ph-H), 7.64 (dd, J = 2.8, 8.8 Hz, 1H, Ph-H), 7.62 (d, J = 2.6
Hz, 1H, H-5), 7.35 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 7.06 (s, 1H, H-3), 4.77-4.87 (m, 1H,
OCH(CH3)2), 2.49 (s, 3H, 11-CH3), 1.35 (s, 3H, OCH(CH3)2), 1.34 (s, 3H,
OCH(CH3)2); 13C NMR (150 MHz, DMSO-d6): δ 156.5 (C-2), 154.8 (C-6), 148.5 (C-
3’), 145.5 (C-4), 144.2 (C-9), 142.3 (C-1’), 132.7 (Ph-C), 130.3 (C-8), 125.5 (C-7),
122.6 (Ph-C), 120.1 (C-10), 117.3 (Ph-C), 117.1 (Ph-C), 104.9 (C-3), 103.9 (C-5), 70.1
(OCH(CH3)2), 25.0 (C-11), 22.3 (s, 2C, OCH(CH3)2). ESI-HRMS (+): m/z [M+H]+
calculated for C19H19ClN3O3+, 372.1109, found, 372.1112.
2-chloro-5-((6-isopropoxy-2-methylquinolin-4-yl)amino)benzoic acid (7u). White
solid; Yield: 57.3 %; HPLC purity: 90.3 % (tR = 21.88 min); mp: 265-267 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 14.70 (br. s., 1H, COOH), 10.78 (s, 1H, NH), 8.23 (d, J = 2.2
Hz, 1H, Ph-H), 8.05 (d, J = 9.2 Hz, 1H, H-8), 7.88 (d, J = 2.4 Hz, 1H, H-5), 7.70-7.73
(m, 1H, Ph-H), 7.67-7.70 (m, 1H, Ph-H), 7.60 (dd, J = 2.2, 9.2 Hz, 1H, H-7), 6.80 (s,
1H, H-3), 4.95-5.05 (m, 1H, OCH(CH3)2), 2.62 (s, 3H, 11-CH3), 1.37 (s, 3H,
OCH(CH3)2), 1.36 (s, 3H, OCH(CH3)2); 13C NMR (150 MHz, DMSO-d6): δ 166.4
(COOH), 156.4 (C-2), 153.4 (C-6), 153.0 (C-4), 137.2 (C-9), 133.7 (Ph-C), 133.0 (Ph-
C), 132.6 (Ph-C), 129.8 (C-8), 129.7 (Ph-C), 128.0 (Ph-C), 126.3 (C-7), 122.0 (Ph-C),
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11
118.1 (C-10), 105.0 (C-3), 100.7 (C-5), 70.8 (OCH(CH3)2), 22.1 (s, 2C, OCH(CH3)2),
19.9 (C-11). ESI-HRMS (+): m/z [M+H]+ calculated for C20H20ClN2O3+, 371.1157,
found, 371.1158.
Butyl 2-chloro-5-((6-isopropoxy-2-methylquinolin-4-yl)amino)benzoate (7v).
White solid; Yield: 44.7 %; HPLC purity: 94.9 % (tR = 24.98 min); mp: 192-194 ºC. 1H
NMR (600 MHz, DMSO-d6): δ 7.77 (d, J = 9.2 Hz, 1H, H-8), 7.72-76 (m, 2H), 7.56-
7.59 (m, 2H), 7.34 (dd, J = 2.5, 9.1 Hz, 1H, H-7), 6.92 (s, 1H, H-3), 4.80-4.89 (m, 1H,
OCH(CH3)2), 4.29 (t, J = 6.4 Hz, 2H, 15-CH2), 2.47 (s, 3H, 11-CH3), 1.65-1.72 (m,
2H), 1.38-1.46 (m, 2H), 1.34 (s, 3H, OCH(CH3)2), 1.33 (s, 3H, OCH(CH3)2), 0.92 (t, J
= 7.4 Hz, 3H, 18-CH3); 13C NMR (150 MHz, DMSO-d6): δ 165.3 (C=O), 156.0 (C-2),
154.8 (C-6), 147.0 (C-4), 142.8 (C-9), 140.6 (C-1’), 132.2 (Ph-C), 131.3 (C-8), 129.4
(Ph-C), 126.2 (Ph-C), 125.6 (C-7), 124.0 (Ph-C), 122.9 (Ph-C), 119.7 (C-10), 104.1 (C-
3), 103.3 (C-5), 70.1 (OCH(CH3)2), 65.5 (COO-CH2), 30.6, 24.5 (C-11), 22.3 (s, 2C,
OCH(CH3)2), 19.2, 14.0. ESI-HRMS (+): m/z [M+H]+ calculated for C24H28ClN2O3+,
427.1783, found, 427.1789.
N-(2,4-dichlorophenyl)-6-methoxy-2-methylquinolin-4-amine (7w). White solid;
Yield: 35.9 %; HPLC purity: 98.5 % (tR = 21.41 min); mp: 256-257 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.01 (s, 1H, H-5), 7.91 (d, J = 9.2 Hz, 1H, H-8), 7.89 (d, J = 2.4
Hz, 1H, Ph-H), 7.59-7.63 (m, 1H, Ph-H), 7.55-7.58 (m, 1H, Ph-H), 7.53 (dd, J = 2.3,
9.1 Hz, 1H, H-7), 6.22 (s, 1H, H-3), 3.95 (s, 3H, OCH3), 2.51 (s, 3H, 11-CH3); 13C
NMR (150 MHz, DMSO-d6): δ 157.6 (C-2), 154.0 (C-6), 152.0 (C-4), 137.4 (C-9),
135.5 (C-1’), 132.7 (Ph-C), 132.4 (Ph-C), 131.0 (C-8), 130.7 (Ph-C), 129.4 (Ph-C),
124.8 (C-7), 124.1 (Ph-C), 118.0 (C-10), 102.7 (C-3), 101.7 (C-5), 56.6 (OCH3), 21.7
(C-11). ESI-HRMS (+): m/z [M+H]+ calculated for C17H15Cl2N2O+, 333.0556, found,
333.0553.
6-ethoxy-N-(4-fluoro-2-methylphenyl)-2-methylquinolin-4-amine (7x). White
solid; Yield: 32.4 %; HPLC purity: 92.3 % (tR = 20.73 min); mp: 197-199 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 10.17 (br. s., 1H, NH), 8.15 (d, J = 2.2 Hz, 1H, H-5), 7.96 (d,
J = 9.4 Hz, 1H, H-8), 7.55 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 7.38 (dd, J = 5.5, 8.6 Hz, 1H,
Ph-H), 7.35 (dd, J = 2.8, 9.6 Hz, 1H, Ph-H), 7.22 (td, J = 2.9, 8.4 Hz, 1H, Ph-H), 6.04
(s, 1H, H-3), 4.25 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.51 (s, 3H, 11-CH3), 2.20 (s, 3H,
14-CH3), 1.42 (t, J = 7.0 Hz, 3H, OCH2CH3); 13C NMR (150 MHz, DMSO-d6): δ 162.2
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12
(d, J = 244.3 Hz, 1C, C-F), 156.9 (C-2), 153.6 (C-6), 153.3 (C-4), 138.8 (d, J = 8.8 Hz,
1C, C-2’), 133.2 (C-8), 130.3 (d, J = 8.8 Hz, 1C, C-6’), 124.4 (C-7), 123.8 (C-1’), 118.4
(d, J = 22.0 Hz, 1C, C-3’), 117.6 (C-10), 114.7 (d, J = 9.9 Hz, 1C, C-5’), 103.6 (C-3),
100.0 (C-5), 64.7 (OCH2CH3), 21.2 (11-CH3), 18.0 (14-CH3), 15.0 (OCH2CH3). ESI-
HRMS (+): m/z [M+H]+ calculated for C19H20FN2O+, 311.1554, found, 311.1557.
4-((6-ethoxy-2-methylquinolin-4-yl)amino)-N-hydroxybenzamide (7y). White
solid; Yield: 30.9 %; HPLC purity: 90.3 % (tR = 19.28 min); mp: 216-218 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 11.32 (br. s., 1H, CONH-OH), 7.99-8.08 (m, 2H), 7.94 (d, J
= 9.2 Hz, 1H, H-8), 7.90-7.93 (m, 1H), 7.51-7.59 (m, 3H), 7.01 (s, 1H, CONH-OH),
6.89 (s, 1H, H-3), 4.25 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.58 (s, 3H, 11-CH3), 1.43 (t, J
= 7.0 Hz, 3H, OCH2CH3); 13C NMR (150 MHz, DMSO-d6): δ 167.3 (C=O), 156.7 (C-
2), 156.5 (C-6), 155.2 (C-1’), 154.6 (C-4), 144.8 (C-9), 131.4 (3C), 128.9 (C-7), 121.5
(2C), 119.5 (C-10), 119.0 (Ph-C), 103.1 (C-3), 102.9 (C-5), 64.4 (OCH2CH3), 23.2 (11-
CH3), 15.0 (OCH2CH3). ESI-HRMS (+): m/z [M-H]- calculated for C19H18N3O3+,
336.1354, found, 336.1356.
N-(3,4-dimethoxyphenyl)-6-isopropoxy-2-methylquinolin-4-amine (7z). White solid;
Yield: 41.0 %; HPLC purity: 94.4 % (tR = 20.05 min); mp: 242-243 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.50 (br. s., 1H, NH), 7.70 (d, J = 2.6 Hz, 1H, H-5), 7.67 (d, J =
9.0 Hz, 1H, H-8), 7.24 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 7.01 (d, J = 8.4 Hz, 1H, Ph-H),
6.92 (d, J = 2.4 Hz, 1H, Ph-H), 6.87 (dd, J = 2.3, 8.4 Hz, 1H, Ph-H), 6.60 (s, 1H, H-3),
4.79-4.86 (m, 1H, CH(CH3)2), 3.79 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 2.37 (s, 3H, 11-
CH3), 1.34 (s, 3H, CH(CH3)2), 1.33 (s, 3H CH(CH3)2); 13C NMR (150 MHz, DMSO-
d6): δ 156.4 (C-2), 154.3 (C-6), 149.8 (Ph-C), 148.4 (C-4), 146.2 (C-9), 144.4 (Ph-C),
134.1 (Ph-C), 130.4 (C-8), 122.0 (C-7), 118.9 (C-10), 116.2 (Ph-C), 112.9 (Ph-C),
109.2 (Ph-C), 103.6 (C-3), 101.1 (C-5), 69.9 (CH(CH3)2), 56.2 (OCH3), 56.0 (OCH3),
25.3 (11-CH3), 22.4 (s, 2C, CH(CH3)2). ESI-HRMS (+): m/z [M-H]- calculated for
C21H25N2O3+, 353.1860, found, 353.1865.
N-(5,6-dichloropyridin-3-yl)-6-methoxy-2-methylquinolin-4-amine (7A). White
solid; Yield: 28.9 %; HPLC purity: 97.9 % (tR = 19.22 min); mp: 242-243 ºC. 1H NMR
(600 MHz, DMSO-d6): δ 8.49 (s, 1H, H-2’), 8.16 (s, 1H, H-4’), 7.84 (d, J = 9.4 Hz, 1H,
H-8), 7.82 (s, 1H, H-5), 7.46 (d, J = 8.6 Hz, 1H, H-7), 7.03 (s, 1H, H-3), 3.94 (s, 3H,
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13
OCH3), 2.54 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6): δ 157.1 (C-2), 155.7 (C-6),
147.8 (C-4), 141.8 (C-9), 141.3 (C-3’), 138.8 (C-6’), 132.2 (C-2’), 131.0 (C-5’), 129.6
(C-8), 128.0 (C-7), 122.8 (C-4’), 119.5 (C-10), 103.9 (C-3), 102.0 (C-5), 56.3 (OCH3),
23.7 (CH3). ESI-HRMS (+): m/z [M+H]+ calculated for C16H14Cl2N3O+, 334.0508,
found, 334.0505.
N-(5,6-dichloropyridin-3-yl)-6-ethoxy-2-methylquinolin-4-amine (7B). White
solid; Yield: 25.7 %; HPLC purity: 94.4 % (tR = 20.56 min); mp: 243-245 ºC. 1H NMR
(600 MHz, CD3OD): δ 8.39 (d, J = 2.4 Hz, 1H, H-2’), 8.09 (d, J = 2.4 Hz, 1H, H-4’),
7.75 (d, J = 9.2 Hz, 1H, H-8), 7.74 (d, J = 2.6 Hz, 1H, H-5), 7.52 (dd, J = 2.6, 9.2 Hz,
1H, H-7), 6.83 (s, 1H, H-3), 4.17 (q, J = 7.0 Hz, 2H, OCH2CH3), 2.55 (s, 3H, CH3),
1.40 (t, J = 7.0 Hz, 3H, OCH2CH3); 13C NMR (150 MHz, CD3OD): δ 158.2 (C-2), 153.4
(C-6), 153.2 (C-4), 145.8 (C-9), 143.7 (C-3’), 135.2 (C-6’), 135.2 (C-2’), 134.5 (C-5’),
130.7 (C-8), 125.5 (C-7), 121.7 (C-4’), 118.2 (C-10), 101.9 (C-3), 101.2 (C-5), 64.3
(OCH2CH3), 19.0 (CH3), 13.5 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for
C17H16Cl2N3O+, 348.0665, found, 348.0662.
Spectra data of compounds 9b~9e
6-butoxy-N-(3,4-dichlorophenyl)-2-methylquinolin-4-amine (9b). White solid;
Yield: 46.2 %; HPLC purity: 94.6 % (tR = 24.96 min); mp: 179-181 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.89 (br. s., 1H, NH), 7.74 (d, J = 9.0 Hz, 1H, H-8), 7.60-7.63 (m,
2H), 7.54 (d, J = 2.4 Hz, 1H, Ph-H), 7.35 (dd, J = 2.5, 8.7 Hz, 1H, Ph-H), 7.33 (dd, J =
2.6, 9.2 Hz, 1H, H-7), 6.96 (s, 1H, H-3), 4.11 (t, J = 6.5 Hz, 2H, 12-CH2), 2.47 (s, 3H,
11-CH3), 1.75-1.80 (m, 2H, 13-CH2), 1.49 (sxt, J = 7.4 Hz, 2H, 14-CH2), 0.97 (t, J =
7.3 Hz, 3H, 15-CH3); 13C NMR (150 MHz, DMSO-d6): δ 156.1 (C-2), 156.1 (C-6),
146.7 (C-4), 143.6 (C-9), 141.9 (C-1’), 132.0 (Ph-C), 131.6 (Ph-C), 129.5 (C-8), 124.7
(C-7), 123.2 (Ph-C), 122.1 (Ph-C), 121.7 (Ph-C), 119.6 (C-10), 103.8 (C-3), 102.3 (C-
5), 68.2 (C-12), 31.2 (C-13), 24.7 (C-11), 19.3 (C-14), 14.2 (C-15). ESI-HRMS (+):
m/z [M+H]+ calculated for C20H21Cl2N2O+, 375.1025, found, 375.1021.
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14
N-(3,4-dichlorophenyl)-2-methyl-6-(pentyloxy)quinolin-4-amine (9c). White solid;
Yield: 55.0 %; HPLC purity: 98.6 % (tR = 25.89 min); mp: 189-191 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.85 (br. s., 1H, NH), 7.73 (d, J = 9.2 Hz, 1H, H-8), 7.58-7.62 (m,
2H), 7.53 (d, J = 2.4 Hz, 1H, Ph-C), 7.35 (dd, J = 2.5, 8.7 Hz, 1H, Ph-C), 7.32 (dd, J =
2.6, 9.2 Hz, 1H, H-7), 6.96 (s, 1H, H-3), 4.10 (t, J = 6.5 Hz, 2H, 12-CH2), 2.46 (s, 3H,
11-CH3), 1.76-1.82 (m, 2H, 13-CH2), 1.42-1.48 (m, 2H, 14-CH2), 1.34-1.41 (m, 2H,
15-CH2), 0.91 (t, J = 7.2 Hz, 3H, 16-CH3); 13C NMR (150 MHz, DMSO-d6): δ 156.4
(C-2), 156.0 (C-6), 146.2 (C-4), 144.3 (C-9), 142.2 (C-1’), 132.0 (Ph-C), 131.5 (Ph-C),
130.1 (C-8), 124.4 (C-7), 122.9 (Ph-C), 121.8 (Ph-C), 121.4 (Ph-C), 119.8 (C-10),
104.1 (C-3), 102.2 (C-5), 68.4 (C-12), 28.9 (C-13), 28.3 (C-14), 25.0 (C-11), 22.4 (C-
15), 14.4 (C-16). ESI-HRMS (+): m/z [M+H]+ calculated for C21H23Cl2N2O+, 389.1182,
found, 389.1178.
N-(3,4-dichlorophenyl)-6-(hexyloxy)-2-methylquinolin-4-amine (9d). White solid;
Yield: 50.2 %; HPLC purity: 98.3 % (tR = 26.68 min); mp: 173-174 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.81 (br. s., 1H, NH), 7.73 (d, J = 9.0 Hz, 1H, H-8), 7.60 (d, J =
8.8 Hz, 1H, Ph-H), 7.58 (d, J = 2.4 Hz, 1H, H-5), 7.52 (d, J = 2.2 Hz, 1H, Ph-H), 7.34
(dd, J = 2.3, 8.7 Hz, 1H, Ph-H), 7.32 (dd, J = 2.5, 9.1 Hz, 1H, H-7), 6.97 (s, 1H, H-3),
4.09 (t, J = 6.4 Hz, 2H, 12-CH2), 2.46 (s, 3H, 11-CH3), 1.76-1.81 (m, 2H, 13-CH2), 1.46
(quin, J = 7.3 Hz, 2H, 14-CH2), 1.31-1.36 (m, 4H), 0.87-0.90 (m, 3H, 17-CH3); 13C
NMR (150 MHz, DMSO-d6): δ 156.6 (C-2), 156.0 (C-6), 145.8 (C-4), 144.8 (C-9),
142.3 (C-1’), 132.0 (Ph-C), 131.5 (Ph-C), 130.5 (C-8), 124.2 (C-7), 122.7 (Ph-C), 121.7
(Ph-C), 121.2 (Ph-C), 119.8 (C-10), 104.3 (C-3), 102.1 (C-5), 68.4 (C-12), 31.5 (C-15),
29.1 (C-13), 25.8 (C-14), 25.3 (C-11), 22.6 (C-16), 14.4 (C-17). ESI-HRMS (+): m/z
[M+H]+ calculated for C22H25Cl2N2O+, 403.1338, found, 403.1337.
N-(3,4-dichlorophenyl)-6-(heptyloxy)-2-methylquinolin-4-amine (9e). White solid;
Yield: 50.2 %; HPLC purity: 98.8 % (tR = 27.34 min); mp: 153-155 ºC. 1H NMR (600
MHz, DMSO-d6): δ 8.81 (br. s., 1H, NH), 7.73 (d, J = 9.0 Hz, 1H, H-8), 7.55-7.63 (m,
2H), 7.52 (s, 1H, Ph-H), 7.29-7.37 (m, 2H), 6.97 (s, 1H, H-3), 4.04-4.14 (m, 2H), 2.46
(s, 3H, 11-CH3), 1.75-1.82 (m, 2H), 1.41-1.49 (m, 2H), 1.32-1.39 (m, 2H), 1.24-1.31
(m, 4H), 0.83-0.90 (m, 3H); 13C NMR (150 MHz, DMSO-d6): δ 156.5 (C-2), 156.0 (C-
6), 145.8 (C-4), 144.8 (C-9), 142.3 (C-1’), 132.0 (Ph-C), 131.5 (Ph-C), 130.5 (C-8),
124.2 (C-7), 122.7 (Ph-C), 121.7 (Ph-C), 121.1 (Ph-C), 119.8 (C-10), 104.3 (C-3),
-
15
102.1 (C-5), 68.4 (C-12), 31.7, 29.2, 28.9, 26.0, 25.3 (C-11), 22.5 (C-17), 14.4 (C-18).
ESI-HRMS (+): m/z [M+H]+ calculated for C23H27Cl2N2O+, 417.1495, found,
417.1492.
Spectra data of compounds 10a~10b Ethyl 4-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)butanoate
(10a). White solid; Yield: 37.6 %; HPLC purity: 95.0 % (tR = 23.59 min); mp: 266-267
ºC. 1H NMR (600 MHz, CDCl3): δ 7.88 (d, J = 9.2 Hz, 1H, H-8), 7.40-7.45 (m, 3H),
7.27-7.30 (m, 1H), 7.21 (dd, J = 2.6, 8.6 Hz, 1H, Ph-H), 6.97 (s, 1H, H-3), 4.18 (q, J =
7.2 Hz, 2H, OCH2CH3), 4.06-4.11 (m, 2H), 2.58 (s, 3H, 11-CH3), 2.48-2.52 (m, 2H),
2.11-2.18 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H, OCH2CH3); 13C NMR (150 MHz, CDCl3):
δ 173.8 (C=O), 156.8 (C-2), 155.8 (C-6), 145.6 (C-4), 144.5 (C-9), 140.7 (C-1’), 133.2
(Ph-C), 131.0 (C-8), 130.5 (Ph-C), 126.2 (C-7), 122.8 (Ph-C), 122.0 (Ph-C), 120.2 (Ph-
C), 119.3 (C-10), 104.0 (C-3), 99.9 (C-5), 66.8 (C-12), 60.9 (OCH2CH3), 30.1 (C-14),
25.2 (C-13), 23.3 (C-11), 14.2 (OCH2CH3). ESI-HRMS (+): m/z [M+H]+ calculated for
C22H23Cl2N2O3+, 433.1080, found, 433.1079.
Methyl 5-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)pentanoate
(10b). White solid; Yield: 33.9 %; HPLC purity: 93.1 % (tR = 23.78 min); mp: 166-167
ºC. 1H NMR (600 MHz, CDCl3): δ 7.88 (d, J = 9.0 Hz, 1H, H-8), 7.43 (d, J = 8.6 Hz,
1H, Ph-H), 7.40 (d, J = 2.6 Hz, 1H, H-5), 7.29 (dd, J = 2.9, 9.2 Hz, 1H, H-7), 7.19 (d,
J = 2.8 Hz, 1H, Ph-H), 7.17 (dd, J = 2.6, 8.6 Hz, 1H, Ph-H), 6.94 (s, 1H, H-3), 3.90-
3.97 (m, 2H, 12-CH2), 3.69 (s, 3H, COO-CH3), 2.57 (s, 3H, 11-CH3), 2.38-2.44 (m,
2H), 1.80-1.83 (m, 2H), 1.72-1.78 (m, 2H); 13C NMR (150 MHz, CDCl3): δ 174.3
(C=O), 156.8 (C-2), 156.1 (C-6), 146.1 (C-4), 144.6 (C-9), 140.8 (C-1’), 133.2 (Ph-C),
131.0 (C-8), 130.3 (Ph-C), 126.4 (C-7), 122.9 (Ph-C), 122.0 (Ph-C), 120.7 (Ph-C),
119.6 (C-10), 104.5 (C-3), 100.2 (C-5), 67.6 (C-12), 51.7 (COO-CH3), 33.5, 28.2, 25.1,
21.4 (C-11). ESI-HRMS (+): m/z [M+H]+ calculated for C22H23Cl2N2O3+, 433.1080,
found, 433.1077.
-
16
Spectra data of compounds 11b~11d
5-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)pentanoic acid
(11b). White solid; Yield: 90.5 %; HPLC purity: 95.6 % (tR = 22.57 min); mp: 217-218
ºC. 1H NMR (600 MHz, DMSO-d6): δ 7.71 (d, J = 9.2 Hz, 1H, H-8), 7.69 (d, J = 2.4
Hz, 1H, H-5), 7.60 (d, J = 2.6 Hz, 1H, Ph-H), 7.56 (d, J = 8.8 Hz, 1H, Ph-H), 7.39 (dd,
J = 2.5, 8.7 Hz, 1H, Ph-H), 7.28 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 6.95 (s, 1H, H-3), 4.10
(t, J = 6.7 Hz, 2H, 12-CH2), 2.44 (s, 3H, 11-CH3), 2.09 (t, J = 7.2 Hz, 2H), 1.76 (quin,
J = 7.0 Hz, 2H), 1.60-1.67 (m, 2H); 13C NMR (150 MHz, DMSO-d6): δ 177.2 (C=O),
156.4 (C-2), 155.8 (C-6), 146.1 (C-4), 144.6 (C-9), 142.5 (C-1’), 131.9 (Ph-C), 131.3
(C-8), 130.2 (Ph-C), 123.9 (C-7), 122.8 (Ph-C), 121.9 (Ph-C), 121.2 (Ph-C), 119.9 (C-
10), 103.9 (C-3), 102.3 (C-5), 68.2 (C-12), 37.1 (CH2-COOH), 28.6, 25.2, 22.7 (C-11).
ESI-HRMS (-): m/z [M-H]- calculated for C21H19Cl2N2O3-, 417.0778, found, 417.0774.
6-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)hexanoic acid (11c).
White solid; Yield: 91.0 %; HPLC purity: 93.5 % (tR = 23.16 min); mp: 165-167 ºC. 1H
NMR (600 MHz, DMSO-d6): δ 7.78 (d, J = 9.2 Hz, 1H, H-8), 7.70 (s, 1H, H-5), 7.64
(d, J = 8.6 Hz, 1H, Ph-H), 7.59 (d, J = 2.4 Hz, 1H, Ph-H), 7.36-7.40 (m, 2H), 6.93 (s,
1H, H-3), 4.12 (t, J = 6.4 Hz, 2H, 12-CH2), 2.49 (s, 3H, 11-CH3), 2.25 (t, J = 7.3 Hz,
2H), 1.77-1.83 (m, 2H), 1.59 (quin, J = 7.5 Hz, 2H), 1.44-1.51 (m, 2H); 13C NMR (150
MHz, DMSO-d6): δ 174.9 (C=O), 156.3 (C-2), 155.8 (C-6), 147.2 (C-4), 141.6 (C-9),
132.1 (C-3’), 131.6 (C-8), 130.8 (C-5’), 125.2 (C-7), 123.7 (Ph-C), 122.5 (Ph-C), 122.1
(Ph-C), 119.5 (C-10), 103.6 (C-3), 102.5 (C-5), 68.4 (C-12), 34.1 (CH2-COOH), 28.9,
25.7, 24.8, 24.2 (C-11). ESI-HRMS (-): m/z [M-H]- calculated for C22H21Cl2N2O3-,
431.0935, found, 431.0929.
7-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)heptanoic acid
(11d). White solid; Yield: 87.8 %; HPLC purity: 97.2 % (tR = 24.19 min); mp: 246-247
ºC. 1H NMR (600 MHz, DMSO-d6): δ 7.72 (d, J = 9.0 Hz, 1H, H-8), 7.65 (d, J = 2.6
Hz, 1H, H-5), 7.58 (d, J = 8.6 Hz, 1H, Ph-H), 7.56 (d, J = 2.6 Hz, 1H, Ph-H), 7.36 (dd,
J = 2.6, 8.6 Hz, 1H, Ph-H), 7.30 (dd, J = 2.6, 9.2 Hz, 1H, H-7), 6.95 (s, 1H, H-3), 4.10
(t, J = 6.4 Hz, 2H, 12-CH2), 2.45 (s, 3H, 11-CH3), 2.16 (t, J = 7.3 Hz, 2H), 1.73-1.81
(m, 2H), 1.52 (quin, J = 7.4 Hz, 2H), 1.44 (quin, J = 7.5 Hz, 2H), 1.31-1.38 (m, 2H); 13C NMR (150 MHz, DMSO-d6): δ 175.7 (C=O), 156.5 (C-2), 155.9 (C-6), 146.0 (C-4),
-
17
144.6 (C-9), 142.4 (C-1’), 131.9 (Ph-C), 131.4 (C-8), 130.3 (Ph-C), 124.1 (C-7), 122.7
(Ph-C), 121.8 (Ph-C), 121.2 (Ph-C), 119.9 (C-10), 104.1 (C-3), 102.3 (C-5), 68.4 (C-
12), 35.0 (CH2-COOH), 29.0, 28.9, 25.8, 25.3, 25.2 (C-11). ESI-HRMS (-): m/z [M-H]-
calculated for C23H23Cl2N2O3-, 445.1091, found, 445.1087.
Spectra data of compounds 12a~12b
4-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)-N-hydroxy-
butanamide (12a). White solid; Yield: 35.5 %; HPLC purity: 90.6 % (tR = 20.75 min);
mp: 177-178 ºC. 1H NMR (600 MHz, CD3OD): δ 7.68 (d, J = 9.4 Hz, 1H, H-8), 7.61
(d, J = 1.7 Hz, 1H, H-5), 7.48-7.51 (m, 2H, Ph-H), 7.37 (dd, J = 2.2, 9.2 Hz, 1H, H-7),
7.28 (dd, J = 2.1, 8.5 Hz, 1H, Ph-H), 6.77 (s, 1H, H-3), 4.09 (t, J = 6.1 Hz, 2H, 12-CH2),
2.46 (s, 3H, 11-CH3), 2.25 (t, J = 7.2 Hz, 2H, 14-CH2), 2.07 (quin, J = 6.6 Hz, 2H, 13-
CH2); 13C NMR (150 MHz, CD3OD): δ 170.9 (C=O), 157.1 (C-2), 154.6 (C-6), 150.6
(C-4), 139.3 (C-9), 138.7 (C-1’), 132.9 (Ph-C), 131.1 (C-8), 128.2 (Ph-C), 125.1 (C-7),
124.6 (Ph-C), 123.8 (Ph-C), 123.1 (Ph-C), 118.6 (C-10), 101.7 (C-3), 101.5 (C-5), 67.4
(C-12), 28.8 (C-14), 24.8 (C-13), 20.8 (C-11). ESI-HRMS (-): m/z [M-H]- calculated
for C20H18Cl2N3O3-, 418.0731, found, 418.0728.
5-((4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-yl)oxy)-N-hydroxy-
pentanamide (12b). White solid; Yield: 50.2 %; HPLC purity: 91.3 % (tR = 21.36 min);
mp: 168-170 ºC. 1H NMR (600 MHz, CD3OD): δ 7.82 (d, J = 9.2 Hz, 1H, H-8), 7.80
(d, J = 2.4 Hz, 1H, H-5), 7.64-7.68 (m, 2H, Ph-H), 7.54 (dd, J = 2.4, 9.2 Hz, 1H, H-7),
7.43 (dd, J = 2.4, 8.6 Hz, 1H, Ph-H), 6.86 (s, 1H, H-3), 4.21 (t, J = 6.1 Hz, 2H, 12-CH2),
2.61 (s, 3H, 11-CH3), 2.23 (t, J = 7.1 Hz, 2H), 1.84-1.95 (m, 4H); 13C NMR (150 MHz,
CD3OD): δ 171.2 (C=O), 157.6 (C-2), 153.7 (C-6), 152.0 (C-4), 138.5 (C-9), 136.6 (C-
1’), 133.0 (Ph-C), 131.3 (C-8), 129.2 (Ph-C), 125.9 (C-7), 124.5 (Ph-C), 123.9 (Ph-C),
123.1 (Ph-C), 118.3 (C-10), 101.8 (C-3), 101.1 (C-5), 68.1 (C-12), 32.0 (C-15), 28.1
(C-13), 22.0 (C-14), 19.9 (C-11). ESI-HRMS (-): m/z [M-H]- calculated for
C21H20Cl2N3O3-, 432.0887, found, 432.0882.
-
18
The 1H and 13C NMR spectra of compounds 2, 3, 7a~7B,
9a~9e, 10a~10d, 11a~11d and 12a~12d
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.62
1.60
1.71
1.08
0.52
1.00
0.99
0.49
1.17
331.
1852
1.19
69
1.88
68
3.75
144.
0347
4.04
664.
05854
.622
6
6.91
466.
9293
7.11
75
7.13
22
10.1
405
The 1H-NMR Spectra of compound 2
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
DMSO
14.9
862
20.1
557
55.7
229
58.4
863
84.7
93411
4.74
62
126.
6530
132.
0121
157.
3641
160.
2952
169.
8979
The 13C-NMR Spectra of compound 2
O
NH
O
2
O
O
NH
O
2
O
-
19
12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.00
0.97
1.00
0.96
1.00
DMSOWater
2.54
12
6.49
317.
4367
7.44
167.
45667
.493
87.
7945
7.80
95
The 1H-NMR Spectra of compound 3
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
DMSO
19.8
641
55.8
687
104.
0717
107.
4330
120.
3606
123.
0657
124.
7281
135.
1766
150.
4738
156.
2486
174.
5863
The 13C-NMR Spectra of compound 3
NH
OO
3
NH
OO
3
-
20
11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.94
3.13
1.00
0.99
0.96
0.89
0.91
1.02
0.98
DMSO
Water
2.59
10
3.97
04
6.88
737.
4902
7.50
067.
5046
7.75
577.
7585
7.76
987.
9519
7.96
728.
0839
The 1H-NMR Spectra of compound 7a /AV6
160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
DMSO
21.0
963
56.7
801
101.
8770
103.
0436
118.
4575
124.
7208
124.
9760
126.
5728
128.
2935
131.
9611
132.
3913
139.
2379
151.
8227
151.
8883
153.
878915
7.86
72
The 13C-NMR Spectra of compound 7a /AV6
6
78
910
5
N1
2
34O
HN
11
1'3'
4'
7a / AV6
Cl
Cl
12
6
78
910
5
N1
2
34O
HN
11
1'3'
4'
7a / AV6
Cl
Cl
12
-
21
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.08
3.14
1.04
0.95
1.13
1.00
1.00
2.02
2.51
72
3.93
57
6.92
027.
4271
7.43
847.
6575
7.76
487.
7687
7.82
227.
8372
The 1H-NMR Spectra of compound 7b
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.7
660
56.4
666
102.
2708
102.
7155
118.
94611
22.4
896
123.
4958
128.
2206
131.
5892
140.
3826
149.
5697
151.
8300
154.
95801
57.3
349
The 13C-NMR Spectra of compound 7b
N
OHN
Cl
Br
7b
N
OHN
Cl
Br
7b
-
22
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.07
3.10
0.99
1.00
2.02
1.00
1.00
0.97
0.48
Water
2.61
753.9
819
6.91
907.
3954
7.62
127.
6374
7.75
417.
9943
8.00
968.
1642
10.6
977
The 1H-NMR Spectra of compound 7c
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
20.2
724
56.9
332
101.
4906
103.
3718
114.
0025
114.
1556
117.
3274
117.
4368
118.
2096
122.
3292
122.
6501
125.
3406
131.
9319
138.
9827
139.
0483
152.
8872
153.
3685
157.
15271
58.1
151
158.
7859
The 13C-NMR Spectra of compound 7c
N
OHN
Cl
F
7c
N
OHN
Cl
F
7c
-
23
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.03
3.04
3.03
1.00
1.00
0.97
1.07
0.88
1.01
0.97
0.40
DMSO
Water
2.39
172.57
72
3.96
99
6.72
467.
34107
.462
07.
56167.57
567.
57907.
9738
7.98
918.
1339
10.4
626
The 1H-NMR Spectra of compound 7d
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
20.1
630
20.5
640
56.8
093
100.
7760
103.
0728
117.
9763
124.
7354
125.
0052
128.
1404130.
5539
137.
167113
7.61
92
153.
0039
153.
2883
157.
9620
The 13C-NMR Spectra of compound 7d
N
OHN CH3
Cl
7d
N
OHN CH3
Cl
7d
-
24
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.96
2.96
2.94
0.96
1.00
1.01
1.03
0.99
1.01
1.06
DMSO
2.46
54
3.87
073.
9251
6.92
067.
1247
7.36
927.
4370
7.45
117.
7291
7.74
997.
7649
The 1H-NMR Spectra of compound 7e
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
24.4
503
56.2
260
56.5
322
101.
7458
102.
9634
107.
5570
115.
2931
119.
2960
122.
0084
129.
0810
130.
6851
141.
3305
143.
1241
147.
8489
155.
5413
156.
6641
The 13C-NMR Spectra of compound 7e
N
OHN
Cl
O
7e
N
OHN
Cl
O
7e
-
25
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.08
3.07
2.00
1.00
2.03
0.98
2.01
0.98
DMSO
Water
1.40
201.
4121
1.42
31
2.47
48
4.17
074.
1817
6.95
547.
3422
7.35
727.
55157.
6331
7.74
567.
7602
The 1H-NMR Spectra of compound 7f
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
15.0
840
24.6
940
64.1
183
102.
2520
103.
8269
119.
6272
121.
6907
122.
1282
123.
2219
124.
7385
129.
5362
131.
5923
132.
0590
141.
8950
143.
5428
146.
6562
155.
9891
156.
1641
The 13C-NMR Spectra of compound 7f
N
OHN
Cl
Cl
7f
N
OHN
Cl
Cl
7f
-
26
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.14
3.23
2.07
0.97
0.97
0.98
2.01
1.02
1.00
0.50
DMSO
Water
1.40
081.
4121
1.42
34
2.46
69
4.15
614.
1671
4.17
844.
1897
6.94
787.
40707
.599
57.
6145
7.66
657.
7340
7.74
93
8.90
71
The 1H-NMR Spectra of compound 7g
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
15.0
955
24.9
3156
4.07
14
102.
1614
103.
8530
119.
6825
121.
9647
122.
2928
126.
20091
31.3
413
142.
0377
144.
0501
146.
3396
155.
9059
156.
2777
The 13C-NMR Spectra of compound 7g
N
OHN
Cl
Br
7g
N
OHN
Cl
Br
7g
-
27
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.12
2.95
2.02
1.01
1.03
2.06
1.00
0.99
1.01
DMSO
1.39
941.
4113
1.42
26
2.48
54
4.16
544.
1770
4.18
864.
2002
6.99
077.
3677
7.57
747.
67457.75
557.
7708
The 1H-NMR Spectra of compound 7h
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
15.0
737
24.2
753
64.1
954
102.
5041
103.
7655
110.
0652
110.
2256
118.
9679
119.
5366
122.
3730
128.
8331
131.
4799
142.
0815
147.
1708
155.
898515
6.10
27
158.
8224
The 13C-NMR Spectra of compound 7h
N
OHN
7h
Cl
F
N
OHN
7h
Cl
F
-
28
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.03
3.12
3.05
2.05
1.01
1.00
1.00
0.95
1.00
0.99
0.89
1.40
521.
4168
1.42
85
2.37
302.
5059
4.19
604.
2076
4.21
924.
2308
6.76
49
7.28
047.39
567.
3986
7.49
677.
5108
7.84
267.
8579
7.90
68
The 1H-NMR Spectra of compound 7i
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
15.0
18420.1
807
22.3
535
64.5
120
101.
4572
103.
0540
118.
5408
123.
4625
126.
8967
130.
3091
137.
2723
138.
4608
150.
6154
154.
42881
56.5
943
The 13C-NMR Spectra of compound 7i
N
OHN
7i
Cl
N
OHN
7i
Cl
-
29
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.13
3.05
3.07
2.01
0.90
0.81
0.99
1.00
0.97
1.00
0.99
0.95
DMSO
Water
1.40
221.
4138
1.42
51
2.43
65
3.86
234.
1608
4.17
244.
1841
4.19
57
6.93
577.
0781
7.30
917.
4044
7.41
857.
6376
7.70
607.
7213
8.71
75
The 1H-NMR Spectra of compound 7j
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
15.1
247
25.2
59756
.473
9
64.0
277
102.
1249
103.
262410
6.95
18
114.
6806
115.
1108
121.
5053
130.
415313
0.61
22
141.
8627
144.
6991
146.
6750
155.
4829
155.
6725
156.
5183
The 13C-NMR Spectra of compound 7j
N
OHN
7j
Cl
O
N
OHN
7j
Cl
O
-
30
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.02
2.93
2.04
0.98
0.98
0.98
0.93
1.00
0.88
0.96
0.67
DMSO
Water
1.42
161.
4332
1.44
48
2.63
17
4.24
974.26
134.
2729
4.28
45
7.01
607.
8581
7.86
827.
8725
7.92
327.
9379
8.00
458.
0197
8.21
84
10.7
968
The 1H-NMR Spectra of compound 7k
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
14.9
278
20.1
484
64.9
464
101.
7093
103.
8603
118.
3482
122.
1543
122.
4313
125.
7635
130.
4664
133.
3100
134.
1995
138.
5452
148.
5270
152.
7997
153.
4195
157.
5245
160.
0036
The 13C-NMR Spectra of compound 7k
N
OHN
7k
Cl
NO2
N
OHN
7k
Cl
NO2
-
31
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.17
3.10
2.06
1.00
0.97
0.97
0.92
1.04
0.99
1.00
DMSOWater
1.32
771.
3393
1.35
09
2.04
40
4.00
854.
0201
4.03
204.
0433
5.96
566.
6434
6.66
206.
8622
6.86
716.
8741
6.87
876.
9010
6.91
507.
2331
7.24
787.
7147
7.71
96
The 1H-NMR Spectra of compound 7l
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
15.3
903
25.1
023
63.2
579
96.9
731
104.
9644
117.
0753
118.
5919
122.
0480
122.
6459
125.
3364
127.
4727
129.
0404
143.
5210
145.
4386
152.
6716
154.
9902
155.
2236
157.
1412
171.
7895
The 13C-NMR Spectra of compound 7l
N
OHN
7l
Cl
OH
O
N
OHN
7l
Cl
OH
O
-
32
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.10
3.96
2.06
3.00
2.06
2.03
0.94
0.96
0.94
0.98
0.97
0.86
0.96
0.88
DMSO
Water
0.90
730.
9198
0.93
201.
3986
1.41
021.
4221
1.66
081.
6846
1.69
651.
7075
2.44
76
4.15
274.1
643
4.17
594.
28624
.296
94.
3076
6.94
837.
3254
7.33
00
7.54
427.
54827.
5543
7.60
967.
6142
7.71
757.
7303
8.87
10
The 1H-NMR Spectra of compound 7m
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.0
091
15.1
0281
9.19
3325
.230
5
30.5
750
64.0
204
65.5
005
102.
0885
103.
6926
119.
740812
1.68
0312
3.36
4612
5.45
7213
1.26
8413
2.12
88
141.
0169
144.
7866
145.
996915
5.79
6515
6.46
73165.
3262
The 13C-NMR Spectra of compound 7m
N
OHN
Cl
O
O
7m
N
OHN
Cl
O
O
7m
-
33
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.26
3.00
2.13
0.92
0.97
1.14
1.01
1.01
0.95
1.07
0.77
0.65
0.76
DMSO
Water
1.40
261.
4142
1.42
58
2.46
08
4.15
734.
1689
4.18
054.
19216.
9425
7.30
987.
3141
7.50
397.
6285
7.73
067.
7456
8.86
94
9.30
27
11.0
533
The 1H-NMR Spectra of compound 7n
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
15.1
028
24.9
972
64.0
641
102.
1687
103.
2113
119.
5585
121.
8334
122.
1615
123.
8823
124.
1885
131.
0715
135.
7380
140.
5065
144.
1668
146.
5583
155.
8475
156.
343316
3.49
61
The 13C-NMR Spectra of compound 7n
7n
N
OHN
ClHN
OOH
7n
N
OHN
ClHN
OOH
-
34
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.14
3.12
3.27
1.08
0.98
1.10
1.02
1.00
1.02
0.98
0.99
0.94
DMSO
Water
1.33
051.
3406
2.45
83
4.78
254.
7923
4.80
234.
8124
4.82
256.95
54
7.31
447.
3187
7.51
527.
5192
7.59
40
7.60
877.
7276
7.74
28
8.79
52
The 1H-NMR Spectra of compound 7o
160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.2
994
25.2
378
70.0
576
103.
8311
104.
1665
119.
8939
121.
2793
122.
3365
122.
7740
124.
2104
130.
5539
131.
5236
131.
9902
142.
2783
144.
6043
145.
8146
154.
6226
156.
5839
The 13C-NMR Spectra of compound 7o
N
OHN
Cl
Cl
7o
N
OHN
Cl
Cl
7o
-
35
12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.90
2.88
3.00
1.05
0.95
1.02
1.03
0.99
1.08
1.08
1.03
0.65
DMSO
Water
1.33
231.
3424
2.46
08
4.78
524.79
534.
8054
4.81
554.
8253
6.93
677.
3236
7.40
157.
5909
7.60
537.
6145
7.65
187.
6557
7.73
068.
8355
The 1H-NMR Spectra of compound 7p
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.2
994
25.0
701
70.0
722
103.
8311
103.
9405
119.
8210
121.
9355
122.
2709
122.
4678
126.
1280
130.
2476
131.
3195
142.
1471
144.
2324
146.
1136
154.
6736
156.
4090
The 13C-NMR Spectra of compound 7p
N
OHN
Cl
7p
Br
N
OHN
Cl
7p
Br
-
36
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.76
2.74
3.00
1.01
1.02
1.07
2.15
1.06
1.11
1.02
0.71
DMSO
Water
1.32
961.
3396
2.46
60
4.78
714.79
714.
8072
4.81
734.
8274
6.98
847.
3245
7.32
827.
5531
7.61
787.
6221
7.73
407.
7492
8.86
27
The 1H-NMR Spectra of compound 7q
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.2
994
25.0
336
70.0
941
104.
0207
104.
2030
109.
5694
112.
6026118.
3773
119.
8866
122.
4021
130.
1966
131.
4070
142.
7231
144.
1814
146.
0480
154.
6736
157.
2037
158.
8297
The 13C-NMR Spectra of compound 7q
N
OHN
Cl
7q
F
N
OHN
Cl
7q
F
-
37
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.75
2.97
3.15
3.24
1.04
1.02
1.00
1.04
1.00
0.96
0.97
1.02
0.64
DMSO
Water
1.33
471.
3448
2.35
322.
4308
4.80
364.81
364.
8237
4.83
354.
8436
6.79
987.
2930
7.32
087.
3245
7.42
697.
6951
7.71
137.
7266
8.78
24
The 1H-NMR Spectra of compound 7r
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
20.1
922
22.3
067
24.9
461
70.0
212
102.
4895
103.
8092
119.
3763
121.
8407
125.
3114
127.
8488
130.
0435
136.
8827
140.
2003
143.
8022
147.
33121
54.5
715
156.
2412
The 13C-NMR Spectra of compound 7r
N
OHN
Cl
7r
N
OHN
Cl
7r
-
38
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.84
2.83
2.97
3.00
1.02
0.91
1.09
0.97
1.04
1.00
1.00
0.96
1.03
DMSO
Water
1.33
691.
3470
2.43
57
3.86
30
4.80
574.
8158
4.82
564.
8356
4.84
576.92
217.
0813
7.30
137.
4058
7.41
987.
6576
7.66
157.
7080
7.72
338.
7014
The 1H-NMR Spectra of compound 7s
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.3
358
25.3
107
55.8
468
56.4
739
70.0
212
99.0
334
103.
2186
103.
8821
107.
0247
114.
7462
115.
1035
119.
6314
122.
1397
130.
1164
130.
5976
141.
8919
144.
6553
146.
5948
154.
4549
155.
4757
156.
5839
The 13C-NMR Spectra of compound 7s
N
OHN
Cl
7s
O
N
OHN
Cl
7s
O
-
39
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.83
2.97
2.78
0.99
0.88
1.02
0.93
1.10
1.00
1.02
0.98
DMSO
Water
1.33
511.
3451
2.48
89
4.79
074.80
084.
8106
4.82
074.
83087
.059
07.
3398
7.35
087.
35507.62
217.
7077
7.75
937.
7743
7.93
44
The 1H-NMR Spectra of compound 7t
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.2
775
24.9
826
70.1
451
103.
9186
104.
9394
117.
0795
120.
1127
122.
6136
125.
4645
130.
2841
132.
7413
142.
3148
144.
2251
145.
4719
148.
4906
154.
8340
156.
4964
The 13C-NMR Spectra of compound 7t
N
OHN
Cl
7t
NO2
N
OHN
Cl
7t
NO2
-
40
15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.88
3.06
3.31
1.01
1.05
1.05
1.03
1.09
1.00
1.00
0.95
0.98
0.83
DMSO
1.35
951.36
96
2.61
66
4.97
444.98
454.
9946
5.00
435.
0144
6.79
957.
5940
7.60
937.69
737.
7077
7.87
827.
8822
8.04
448.
0597
8.22
3510.7
783
14.7
049
The 1H-NMR Spectra of compound 7u
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
19.9
224
22.1
244
70.7
795
100.
7104
104.
9904
118.
1003
121.
9501
126.
2884
128.
0165
129.
6935
129.
8393
132.
5517
133.
0183
133.
7256
137.
1598
152.
9747
153.
3830
156.
3579
166.
4272
The 13C-NMR Spectra of compound 7u
N
OHN
Cl
7u
COOH
N
OHN
Cl
7u
COOH
-
41
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.96
2.68
2.80
2.20
1.96
2.96
2.03
0.96
0.91
1.00
1.85
0.90
1.00
1.07
DMSO
0.90
450.
9170
0.92
931.
3308
1.34
091.
4224
1.66
841.
6816
1.69
322.
4653
4.28
384.
2945
4.30
524.
8344
4.84
454.
8546
4.86
474.
8741
6.91
567.
3346
7.34
967.
5751
7.74
747.
7636
7.77
89
The 1H-NMR Spectra of compound 7v
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.0
091
19.1
860
22.2
775
24.4
941
30.5
605
65.5
224
70.1
233
103.
2988
104.
0571
119.
6533
122.
8761
123.
9771
126.
157213
1.33
4013
2.16
53
140.
6305
143.
1752
147.
03231
54.8
340
155.
97881
65.2
898
The 13C-NMR Spectra of compound 7v
N
OHN
Cl
7v
O
O
N
OHN
Cl
7v
O
O
-
42
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.37
3.09
0.91
1.00
1.03
1.03
0.93
0.98
0.98
2.50
703.94
96
6.22
21
7.52
177.
5370
7.55
627.
5703
7.61
647.
8856
7.88
967.
9025
7.91
778.
0118
The 1H-NMR Spectra of compound 7w
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
21.6
608
56.6
228
101.
6833
102.
6822
118.
0450
124.
1479
124.
7603
129.
4122
130.
6736
131.
0309
132.
4162
132.
6642
135.
4567
137.
3525
152.
0081
154.
0496
157.
6151
The 13C-NMR Spectra of compound 7w
N
OHN
Cl
Cl
7w
N
OHN
Cl
Cl
7w
-
43
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.39
3.32
3.40
2.26
1.06
1.09
1.05
1.06
1.01
1.03
1.00
0.33
1.41
131.
4229
1.43
45
2.20
482.
5095
4.22
954.
2411
4.25
274.
2644
6.04
31
7.22
507.
3671
7.37
637.
3815
7.55
657.
56087.
9571
7.97
278.
1463
8.15
00
10.1
740
The 1H-NMR Spectra of compound 7x
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.9
934
17.9
756
21.1
838
64.6
985
100.
0032
103.
5540
114.
5494
114.
6952
117.
6263
118.
3555
124.
4146
130.
2112
130.
2695
133.
1788
138.
7056
138.
7639
153.
3320
153.
60181
56.8
902
160.
6161
162.
2347
The 13C-NMR Spectra of compound 7x
N
OHN
F
7x
N
OHN
F
7x
-
44
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.00
3.10
1.91
0.59
2.95
1.20
0.85
1.73
0.46
DMSO
1.41
541.
4270
1.43
86
2.58
18
4.22
974.2
3524
.241
0
4.25
266.8
860
7.52
927.54
33
7.58
217.
9048
7.91
88
8.05
97
11.3
180
The 1H-NMR Spectra of compound 7y
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
15.0
299
23.1
5976
4.37
77
102.
8978
103.
0655
118.
9752
119.
4929
121.
4907
128.
8550
131.
4361
144.
8376
154.
6444
155.
1621
156.
5110
156.
6641
167.
3460
The 13C-NMR Spectra of compound 7y
N
OHN
NH
OOH
7y
N
OHN
NH
OOH
7y
-
45
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.79
2.94
3.06
2.96
3.14
1.01
1.02
1.02
0.99
1.00
0.97
0.97
1.00
0.97
DMSO
Water
1.33
431.
3444
2.36
92
3.76
903.
7852
4.80
194.
8119
4.82
204.
8321
4.84
22
6.59
716.
9222
7.00
757.
0215
7.25
047.65
837.
6733
7.69
867.
7029
8.50
23
The 1H-NMR Spectra of compound 7z
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.3
577
25.3
180
56.0
072
56.1
968
69.9
118
101.
0677
103.
6197
109.
1902
112.
9015
116.
2483
118.
9023
122.
0230
130.
3716
134.
0537
144.
4293
146.
2084
148.
4176
149.
7520
154.
2580
156.
4308
The 13C-NMR Spectra of compound 7z
N
OHN
O
7z
O
N
OHN
O
7z
O
-
46
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.34
3.27
0.98
1.00
0.78
1.16
0.99
1.03
Water
2.53
593.94
03
7.02
50
7.46
667.82
177.
8314
7.84
708.
1584
8.48
90
The 1H-NMR Spectra of compound 7A
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
DMSO
23.6
774
56.3
353
101.
9791
103.
8821
119.
5221
122.
7886
129.
6497
132.
2163
138.
7785
141.
2648
141.
7607
155.
6579
157.
1016
The 13C-NMR Spectra of compound 7A
N
OHN
N
Cl
Cl
7A
N
OHN
N
Cl
Cl
7A
-
47
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.08
3.13
2.11
1.00
1.02
0.83
1.17
0.96
0.93
Methanol
1.39
031.
4019
1.41
35
2.55
21
4.15
024.
1618
4.17
344.
1850
6.83
46
7.52
957.73
647.7
434
8.08
658.
0905
8.38
668.
3906
The 1H-NMR Spectra of compound 7B
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
13.5
279
19.0
183
64.3
485
101.
1844
101.
8552
118.
2169
121.
724112
5.52
2813
0.70
7013
4.53
49135
.220
3
143.
7366
145.
8000
153.
2081
153.
3903
158.
1807
The 13C-NMR Spectra of compound 7B
-
48
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.07
2.10
3.11
2.01
1.00
2.12
1.03
1.06
1.00
1.05
1.02
141.
0336
1.04
591.
78561.
79721
.808
91.
8208
1.83
241.
8443
2.48
54
4.07
374.
0844
4.09
54
6.94
457.
3766
7.57
927.
5832
7.62
417.
6385
7.76
477.
7800
The 1H-NMR Spectra of compound 9a
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
10.9
686
22.5
327
24.4
066
70.0
430
102.
4530
103.
6780
119.
5658
121.
9063
122.
3219
123.
4667
124.
9541
131.
5674
132.
0559
141.
7388
142.
9929
147.
0687
155.
9277
156.
2048
The 13C-NMR Spectra of compound 9a
N
OHN
Cl
Cl
9a
N
OHN
Cl
Cl
9a
-
49
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.02
2.04
2.00
3.10
1.94
1.00
0.99
1.09
0.99
2.03
1.02
0.61
DMSO
Water 0.9
541
0.96
630.
9785
1.46
071.
4851
1.49
771.
5224
1.76
471.
7776
1.78
922.
4654
4.09
784.
1084
4.11
946.9
573
7.32
007.
5384
7.60
057.
61097
.614
57.
7313
7.74
62
8.89
43
The 1H-NMR Spectra of compound 9b
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.2
060
19.2
953
24.6
618
31.2
386
68.1
765
102.
3364
103.
8457
119.
6387
121.
6949
122.
1324
123.
2479
124.
7208
129.
4747
131.
5528
132.
0413
141.
9065
143.
5616
146.
711515
6.14
65
The 13C-NMR Spectra of compound 9b
N
OHN
Cl
Cl
9b
N
OHN
Cl
Cl
9b
-
50
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.07
2.05
2.07
2.05
3.06
1.93
0.96
1.00
0.97
1.00
1.94
1.00
0.76
DMSO
Water
0.90
240.
9146
0.92
651.
3449
1.36
871.
3812
1.44
721.
7696
1.79
341.
8050
1.81
632.
4626
4.08
494.
0956
4.10
66
6.95
94
7.52
537.
5292
7.59
597.
6105
7.72
737.
7425
8.84
93
The 1H-NMR Spectra of compound 9c
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.3
883
22.3
869
25.0
336
28.2
710
28.8
689
68.3
952
102.
1979
104.
0863
119.
7700
121.
3595
122.
8907
124.
3562
130.
1164
131.
5236
132.
0121
142.
1908
144.
3199
146.
1792
156.
0298
156.
3506
The 13C-NMR Spectra of compound 9c
N
OHN
Cl
Cl
9c
N
OHN
Cl
Cl
9c
-
51
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.01
3.87
2.06
2.04
3.04
1.97
1.00
1.02
1.00
0.95
1.01
1.00
0.99
0.88
DMSO
Water
0.87
450.
8861
1.32
581.
3319
1.33
741.
4630
1.78
391.
7958
2.46
04
4.08
234.0
930
4.10
376.9
672
7.33
887.51
797.
5744
7.59
217.
6068
7.72
537.
7403
8.80
86
The 1H-NMR Spectra of compound 9d
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.3
810
22.5
546
25.7
555
29.1
45931.4
865
68.3
660
102.
1031
104.
2686
119.
821012
1.16
2612
2.68
6512
4.15
2113
0.52
4713
1.50
9013
1.99
0214
2.29
2914
4.79
3914
5.80
73
155.
9642
156.
5548
The 13C-NMR Spectra of compound 9d
N
OHN
Cl
Cl
9d
N
OHN
Cl
Cl
9d
-
52
12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.00
4.07
2.27
2.04
1.97
3.00
2.03
0.98
1.97
0.97
2.00
0.96
0.96
DMSO
Water
0.86
80
1.28
541.
4498
1.77
131.
7811
2.46
19
4.08
72
6.96
967.
30677.
5190
7.57
537.
5896
7.60
407.
7274
7.74
248.80
67
The 1H-NMR Spectra of compound 9e
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.4
174
22.5
400
26.0
471
28.9
491
31.7
271
68.3
515
102.
0885
104.
2613
119.
8210
121.
1480
122.
6719
124.
1521
130.
5247
131.
5090
131.
9902
142.
2856
144.
7939
145.
7928
155.
9569
156.
5475
The 13C-NMR Spectra of compound 9e
N
OHN
Cl
Cl
9e
N
OHN
Cl
Cl
9e
-
53
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.94
2.00
2.01
2.96
2.00
1.96
0.94
1.10
1.00
2.99
1.00
1.26
221.
2696
1.28
151.
2934
2.13
652.
1441
2.15
542.
49582
.504
12.
5823
4.06
464.0
762
4.08
844.
1630
4.17
494.
1868
4.19
87
6.97
057.
2205
7.27
007.
4194
7.43
447.
8707
7.88
60
The 1H-NMR Spectra of compound 10a
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.2
060
23.2
618
25.2
232
30.1
011
60.9
289
66.8
494
99.8
646
104.
0134
119.
27421
20.2
002
122.
0230
122.
7813
126.
2374
130.
4591
130.
9768
133.
1933
140.
7180
144.
5387
145.
625115
5.78
1915
6.83
91
173.
8425
The 13C-NMR Spectra of compound 10a
N
OHN
Cl
Cl
O
O
10a
N
OHN
Cl
Cl
O
O
10a
-
54
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
1.94
1.89
2.05
3.07
2.94
2.02
0.97
1.16
1.15
1.11
0.97
1.04
1.00
CHLOROFORM-d
1.76
271.
8165
1.82
481.
8391
2.40
052.41
212.
5664
3.68
513.
9433
3.95
31
6.94
337.
1756
7.27
007.
3980
7.40
237.
4222
7.43
657.
8747
7.88
97
The 1H-NMR Spectra of compound 10b
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
21.3
661
25.0
84728
.205
4
33.5
062
51.7
345
67.6
223
100.
1636
104.
5457
119.
5731
120.
6887
122.
9490
126.
4197
130.
3132
131.
0497
133.
2298
140.
8274
144.
5605
146.
08441
56.1
465
156.
8100
174.
2509
The 13C-NMR Spectra of compound 10b
N
OHN
Cl
ClO
O
10b
N
OHN
Cl
ClO
O
10b
-
55
12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.04
2.22
2.28
2.08
3.12
2.91
2.05
1.00
2.03
1.01
0.96
0.99
1.00
CHLOROFORM-d
1.50
391.
7022
1.71
481.
7279
1.82
231.
8330
2.35
652.3
687
2.58
11
3.68
02
4.00
844.
0188
6.91
897.
1533
7.27
007.
3788
7.38
317.
4323
7.44
667.
8915
7.90
68
The 1H-NMR Spectra of compound 10c
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
23.5
308
24.4
859
27.7
233
32.8
928
50.5
962
66.9
725
99.3
533
103.
5313
118.
50761
19.7
034
121.
9491
125.
4927
129.
2478
130.
0425
132.
2299
139.
6962
143.
4221
144.
982515
5.33
6215
5.70
80
173.
2947
The 13C-NMR Spectra of compound 10c
N
OHN
Cl
Cl
O
O
10c
N
OHN
Cl
Cl
O
O
10c
-
56
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.00
2.04
2.02
2.01
1.98
2.06
3.04
1.99
2.09
0.98
1.03
1.00
1.00
0.99
0.99
1.00
CHLOROFORM-d
1.23
811.
2500
1.26
191.
3771
1.66
131.
8064
1.82
942.
3027
2.31
492.
5753
3.97
143.
98214.
1178
4.12
944.
1413
6.91
317.
1890
7.27
007.
3672
7.42
527.
4396
7.88
827.
9034
The 1H-NMR Spectra of compound 10d
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
14.2
424
24.7
857
25.0
919
28.6
866
28.8
470
34.2
280
60.3
529
68.1
765
100.
1854
104.
5092
119.
4856
120.
7835
121.
8188
123.
0365
126.
5947
130.
3351
131.
0788
133.
2735
140.
6742
144.
4220
145.
975115
6.46
0015
6.69
33
174.
0394
The 13C-NMR Spectra of compound 10d
N
OHN
Cl
ClO
O
10d
N
OHN
Cl
ClO
O
10d
-
57
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.00
2.10
2.91
1.95
1.02
2.04
0.98
0.99
0.97
1.00
DMSO
WATER
2.00
552.01
712.02
842.
4372
2.44
922.
4895
4.13
384.
1444
4.15
51
6.92
577.
39027
.592
87.
5971
7.63
897.
6536
7.78
257.
7978
The 1H-NMR Spectra of compound 11a
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
23.9
618
24.6
691
30.5
969
67.7
171
102.
5187
103.
3426
119.
3325
122.
4167
122.
6865
123.
9698
125.
5010
131.
6549
132.
1215
141.
2940
142.
1179
147.
7468
155.
7965
156.
190217
4.60
08
The 13C-NMR Spectra of compound 11a
N
OHN
Cl
Cl
HO
O
11a
N
OHN
Cl
Cl
HO
O
11a
-
58
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.01
1.99
1.97
3.01
2.01
1.00
0.96
0.97
1.00
0.98
0.94
1.02
DMSO
Water
1.63
511.
6473
1.74
941.
7616
2.07
942.09
132.
1033
2.44
37
4.09
014.10
144.
1124
6.95
177.
39757.
5488
7.56
347.
6023
7.68
817.
6994
7.71
47
The 1H-NMR Spectra of compound 11b
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
22.6
858
25.1
649
28.6
283
37.0
789
68.2
494
102.
2635
103.
8821
119.
915812
1.18
4512
2.75
9412
3.94
7913
0.21
85131
.348
613
1.90
2814
2.48
9814
4.61
1614
6.14
27
155.
7892
156.
4162
177.
2257
The 13C-NMR Spectra of compound 11b
N
OHN
Cl
ClHO
O
11b
N
OHN
Cl
ClHO
O
11b
-
59
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.06
2.05
2.02
2.06
3.07
2.03
0.98
2.02
0.98
1.00
0.95
1.00
DMSO
Water
1.47
411.
4860
1.58
071.
5933
1.78
521.
7977
2.24
082.
2530
2.48
61
4.10
444.
1151
4.12
586.93
287.
3771
7.39
177.
5839
7.63
407.
6484
7.77
187.
7871
The 1H-NMR Spectra of compound 11c
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
24.2
243
24.7
638
25.7
044
28.8
98034
.111
3
68.4
463
102.
5333
103.
5613
119.
4929
122.
4532
123.
6563
125.
1583
130.
8455
131.
6111
132.
0705
141.
5784
147.
2437
155.
8475
156.
2558
174.
9217
The 13C-NMR Spectra of compound 11c
N
OHN
Cl
Cl
HO
O
11c
N
OHN
Cl
Cl
HO
O
11c
-
60
12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.01
2.02
2.01
2.00
2.00
2.90
1.99
1.00
1.00
1.02
0.97
1.00
1.00
0.98
DMSO
Water
1.33
961.
4448
1.50
531.
5178
1.76
382.
14692
.159
22.
1714
2.44
95
4.08
644.0
971
4.10
78
6.95
177.
29827
.559
87.
5641
7.57
327.
6496
7.71
387.
7288
The 1H-NMR Spectra of compound 11d
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
25.1
649
25.2
597
25.8
430
28.9
126
29.0
366
35.0
009
68.3
587
102.
3145
104.
1446
119.
8866
121.
1772
122.
7230
124.
0719
130.
28411
31.4
434
131.
9392
142.
3877
144.
6334
146.
033415
5.94
2315
6.47
46
175.
7456
The 13C-NMR Spectra of compound 11d
N
OHN
Cl
ClHO
O
11d
N
OHN
Cl
ClHO
O
11d
-
61
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.15
1.88
3.07
2.08
1.00
1.00
1.03
1.95
0.87
0.99
Methanol
2.04
292.0
5422.06
522.
2336
2.24
552.
4634
4.08
074.
0908
4.10
09
6.76
767.
2843
7.38
037.
4912
7.50
59
7.67
027.
6858
The 1H-NMR Spectra of compound 12a
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
20.8
338
24.7
638
28.8
105
67.3
963
101.
4614
101.
6802
118.
5596
123.
0511
123.
7948
125.
0708
128.
2352
131.
1226
132.
8871
138.
6618
139.
2816
150.
6123
154.
578815
7.09
43
170.
8677
The 13C-NMR Spectra of compound 12a
N
OHN
Cl
Cl
NH
OHO
12a
N
OHN
Cl
Cl
NH
OHO
12a
-
62
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
4.09
1.73
3.18
1.96
0.96
1.01
1.00
2.01
0.91
1.06
Water
Methanol
1.86
891.
8805
1.90
491.
9156
2.22
122.
2328
2.24
472.
6126
4.20
404.
2144
4.22
42
6.86
167.
4259
7.44
037.
5521
7.65
607.
8125
7.82
78
The 1H-NMR Spectra of compound 12b
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
19.9
297
21.9
785
28.1
106
31.9
531
68.1
473
101.
1260
101.
7968