supporting information4 spectra data of compounds...

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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

4

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


(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


(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-

5

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


(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


(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;


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;


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


(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;


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


(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



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;


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



9

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



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



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.

10

N-(4-chloro-3-methoxyphenyl)-6-isopropoxy-2-methylquinolin-4-amine (7s).


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


(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


(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),

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).


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;


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


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



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

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


(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;



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


(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,

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


(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;


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.

14

N-(3,4-dichlorophenyl)-2-methyl-6-(pentyloxy)quinolin-4-amine (9c). White solid;



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;



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


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;



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).


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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



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


N

OHN

Cl

Cl

9b

N

OHN

Cl

Cl

9b

50


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



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


N

OHN

Cl

Cl

9c

N

OHN

Cl

Cl

9c

51


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



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


N

OHN

Cl

Cl

9d

N

OHN

Cl

Cl

9d

52


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


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


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



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


N

OHN

Cl

Cl

O

O

10a

N

OHN

Cl

Cl

O

O

10a

54


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



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


N

OHN

Cl

ClO

O

10b

N

OHN

Cl

ClO

O

10b

55


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



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


N

OHN

Cl

Cl

O

O

10c

N

OHN

Cl

Cl

O

O

10c

56


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



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


N

OHN

Cl

ClO

O

10d

N

OHN

Cl

ClO

O

10d

57


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



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


N

OHN

Cl

Cl

HO

O

11a

N

OHN

Cl

Cl

HO

O

11a

58


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



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


N

OHN

Cl

ClHO

O

11b

N

OHN

Cl

ClHO

O

11b

59


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



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


N

OHN

Cl

Cl

HO

O

11c

N

OHN

Cl

Cl

HO

O

11c

60


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



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


N

OHN

Cl

ClHO

O

11d

N

OHN

Cl

ClHO

O

11d

61


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



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


N

OHN

Cl

Cl

NH

OHO

12a

N

OHN

Cl

Cl

NH

OHO

12a

62


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



19.9

297

21.9

785

28.1

106

31.9

531

68.1

473

101.

1260

101.

7968

supporting information4 spectra data of compounds...

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