Vol. 28, No. 10 (2016)
Novel Substituted Phenylamine Derivatives of 6,7-Dimethoxy-quinazolines as Potent Inhibitors 2125
168.15 (NH2-C=NO), 172 (C=O). LC-MS (ESI, m/z): 520.7
(M + 1)+. Anal. calcd. for C30H25N5O4: C, 69.35; H, 4.85; N,
13.48. Found: C, 69.42; H, 4.98; N, 13.71.
98.66 (isoxazole C), 102.7 (quinazoline C), 107.5 (quinazoline
C), 110.11 (quinazoline C), 117.25 (ArC), 125.62 (ArC), 128.13
(ArC), 139.6 (ArC), 143.4 (quinazoline C), 147.2 (quinazoline
C), 150.2 (isoxazole C), 153.5 (quinazoline C), 154 (quinazoline,
N=CHN), 156.5 (quinazoline, N=C-NH), 158.9 (isoxazole C),
167 (NH2-C=NO), 173 (C=O). LC-MS (ESI, m/z): 475.6 (M
+ 1)+.Anal. calcd. for C24H22N6O5: C, 60.75; H, 4.67; N, 17.71.
Found: C, 60.94; H, 4.52; N, 17.73.
N-[4-(6,7-Dimethoxy-quinazolin-4-ylamino)phenyl]-
[(E)-hydroxyiminomethyl]-3,4-dimethoxy-benzamide (7e):
Starting from 0.24 g of 3,4-dimethoxybenzoic acid (e) the title
compound 7e was obtained. Brown solid;Yield: 0.33 g (45 %);
m.p.: 145-146 °C; IR (ATR, νmax, cm-1): 3307.26 (N-H),
3077.40 (Ar-CH), 1712.69 (C=O), 1583.62 (Ar-C=C), 1246.25
(C-O). 1H NMR (DMSO-d6 300 MHz) δ (ppm): 3.86 (s, 3H,
-OCH3), 3.95 (s, 3H, -OCH3), 3.98 (s, 3H, -OCH3), 6.90 (bs,
2H, -NH2), 7.08 (d, J = 6.6 Hz, 2H, ArH), 7.22 (s, 1H, ArH),
7.6 (s, 1H, ArH),7.79-7.89 (m, 4H, ArH), 7.95 (d, J = 6.3 Hz,
2H, ArH), 8.53 (s, 1H, -N=CH), 9.65 (bs, 1H, NH). 13C NMR
(DMSO-d6 100 MHz) δ: 56.27 (CH3, -OCH3), 56.56 (CH3,
-OCH3), 56.65 (CH3, -OCH3), 56.75 (CH3, -OCH3), 102.26
(quinazoline C), 107.3 (quinazoline C), 109.6 (quinazoline C),
116.5 (ArC), 117 (ArC), 120.5 (ArC), 122.5 (ArC), 123.5
(ArC), 124 (ArC), 127.4 (ArC), 139.5 (ArC), 143.4 (quinazoline
C), 146.9 (quinazoline C), 148.2 (ArC), 153.2 (ArC), 153.7
(quinazoline, N=CHN), 153.9 (quinazoline C), 156.4 (quina-
zoline, N=C-NH), 166.7 (NH2-C=NO), 174 (C=O). LC-MS
(ESI, m/z): 504.7 (M + 1)+. Anal. calcd. for C26H25N5O6: C,
62.02; H, 5.00; N, 13.91. Found: C, 62.15; H, 5.17; N, 13.98.
4-tert-Butyl-N-[4-(6,7-dimethoxy-quinazolin-4-
ylamino)phenyl]-[(E)-hydroxyiminomethyl]benzamide
(7f): Starting from 0.25 g of 4-tert-butylbenzoic acid (f) the title
compound 7f was obtained. Off-white solid;Yield: 0.59 g (81
%); m.p.: 190-191 °C; IR (ATR, νmax, cm-1): 3440.62 (N-H),
3009.65 (Ar-CH), 1720.18 (C=O), 1509.34 (Ar-C=C), 1237.62
(C-O). 1H NMR (DMSO-d6 300 MHz) δ (ppm): 1.33 (s, 9H,
-(CH3)3), 3.94 (s, 3H, -OCH3), 3.98 (s, 3H, -OCH3), 6.89 (bs,
2H, -NH2), 7.22 (s, 1H, ArH), 7.50 (d, J = 6.3 Hz, 2H, ArH),
7.81 (d, J = 6.6 Hz, 2H, ArH), 7.88 (s, 1H, ArH), 7.96 (d, J =
6.6 Hz, 2H, ArH), 8.53 (s, 1H, -N=CH), 9.64 (bs, 1H, NH).
13C NMR (DMSO-d6 100 MHz) δ: 31.7 (CH3, -(CH3)3), 35.1
(C, -C(CH3)3) 56.28 (CH3, -OCH3), 56.68 (CH3, -OCH3), 102.28
(quinazoline C), 107.69 (quinazoline C), 109.58 (quinazoline
C), 121.3 (ArC), 122.8 (ArC), 125.2 (ArC), 128.8 (ArC), 129.1
(ArC), 129.9 (ArC), 139.8 (ArC), 143.6 (quinazoline C), 146.9
(quinazoline C), 151.1 (ArC), 153.1 (quinazoline C), 154.3
(quinazoline, N=CHN), 156.3 (quinazoline, N=C-NH), 167.5
(NH2-C=NO), 170 (C=O). LC-MS (ESI, m/z): 500.7 (M + 1)+.
Anal. calcd. for C28H29N5O4: C, 67.32; H, 5.85; N, 14.02. Found:
C, 67.47; H, 5.64; N, 14.14.
N-[4-(6,7-Dimethoxy-quinazolin-4-ylamino)phenyl]-
[(E)-hydroxyiminomethyl]-2-(1H-indol-3-yl)acetamide
(7h): Starting from 0.245 g of indole-3-aceticacid (h) the title
compound 7h was obtained. Brown solid; Yield: 0.25 g (35
%); m.p.: 162-163 °C; IR (ATR, νmax, cm-1): 3343.76 (N-H),
3011.66 (Ar-CH), 1734.96 (C=O), 1582.98 (Ar-C=C), 1241.22
(C-O). 1H NMR (DMSO-d6 300 MHz) δ (ppm): 3.34 (s, 2H,
-OCOCH2), 3.94 (s, 3H, -OCH3), 3.97 (s, 3H, -OCH3), 6.77
(bs, 2H, -NH2), 6.98-7.17 (m, 2H, ArH), 7.21 (s, 1H, ArH),
7.30 (s, 1H, indole-H), 7.36 (d, J = 8.1 Hz, 1H, ArH), 7.6 (d, J
= 7.5 Hz, 1H,ArH),7.71-7.74 (m, 2H,ArH), 7.87 (s, 1H,ArH),
7.91 (d, J = 8.8 Hz, 2H, ArH), 8.51 (s, 1H, -N=CH), 9.62 (bs,
1H, NH), 10.98 (bs, 1H, indole-NH); 13C NMR (DMSO-d6 75
MHz) δ: 30.12 (CH2, indole-CH2), 56.23 (CH3, -OCH3), 56.65
(CH3, -OCH3), 102.28 (quinazoline C), 107.63 (quinazoline
C), 109.43 (indole C), 111.83 (quinazoline C), 115.47 (indole
C), 118.90 (Ar C), 119.01 (indole C), 121.48 (indole C) 121.65
(indole C), 124.57 (indole C), 126.24 (ArC), 127.34 (Ar C),
127.6 (indole C), 136.52 (indole C), 142.07 (quinazoline C),
147.54 (Ar C), 149.42 (quinazoline C), 153.11 (quinazoline
C), 154.77 (quinazoline, N=CHN), 156.50 (quinazoline, N=C-
NH), 156.82 (NH2-C=NO), 169.68 (C=O). LC-MS (ESI, m/z):
497.7 (M + 1)+.Anal. calcd. for C27H24N6O4: C, 65.31; H, 4.87;
N, 16.93. Found: C, 65.48; H, 4.80; N, 17.09.
Cyclopropanecarboxylic acid [4-(6,7-dimethoxy-
quinazolin-4-ylamino)phenyl]-[(E)-hydroxyiminomethyl]-
amide (7i): Starting from 0.12 g of cyclopropane carboxylic
acid (i) the title compound 7i was obtained. Off-white solid;
Yield: 0.36 g (60 %); m.p.: 195-196 °C; IR (ATR, νmax, cm-1):
3313.14 (N-H), 3312.86 (O-H), 3012.95 (Ar-CH), 1650.12
(C=O), 1592.29 (Ar C=C), 1190.82 (C-O). 1H NMR (DMSO-
d6 300 MHz) δ (ppm): 0.87-0.92 (m, 4H), 1.89-1.93 (m, 1H),
3.94 (s, 3H, -OCH3), 3.97 (s, 3H, -OCH3), 6.8 (bs, 2H, -NH2),
7.21 (s, 1H, ArH), 7.74 (d, J = 6.6 Hz, 2H, ArH), 7.87 (s, 1H,
ArH), 7.92 (d, J = 6.6 Hz, 2H, ArH), 8.51 (s, 1H, -N=CH),
9.61 (bs, 1H, NH). 13C NMR (DMSO-d6 100 MHz) δ: 8.6
(cyclopropane C), 13.4 (cyclopropane C), 56.31 (CH3, -OCH3),
56.63 (CH3, -OCH3), 102.32 (quinazoline C), 107.71 (quinazoline
C), 109.58 (quinazoline C), 121.4 (ArC), 122.81 (ArC), 125.2
(ArC), 140.1 (ArC), 143.58 (quinazoline C), 146.8 (quinazoline
C), 153.3 (quinazoline C), 154.7 (quinazoline, N=CHN), 158.1
(quinazoline, N=C-NH), 167.6 (NH2-C=NO), 182 (C=O).
LC-MS (ESI, m/z): 408.6 (M + 1)+.Anal. calcd. for C21H21N5O4:
C, 61.91; H, 5.20; N, 17.19. Found: C, 61.98; H, 5.28; N,
17.37.
5-Cyclopropyl-isoxazole-3-carboxylic acid [4-(6,7-
dimethoxy-quinazolin-4-ylamino)phenyl]-[(E)-hydroxy-
iminomethyl]amide (7g): Starting from 0.214 g of 5-cyclo-
propyl-3-isoxazolecarboxylic acid (g) the title compound 7g
was obtained. Light brown solid; Yield: 0.36 g (52 %); m.p.:
151-152 °C; IR (ATR, νmax, cm-1): 3257.90 (N-H), 3010.4 (Ar-
CH), 1743.01 (C=O), 1507.88 (Ar-C=C), 1580.82 (Ar-C=C),
1233.21 (C-O). 1H NMR (DMSO-d6 300 MHz) δ (ppm): 3.95
(s, 3H, -OCH3), 3.98 (s, 3H, -OCH3), 6.97 (bs, 2H, -NH2),
7.23 (s, 1H, ArH), 7.79 (d, J = 8.4 Hz, 2H, ArH), 7.89 (s, 1H,
ArH), 7.97 (d, J = 8.1 Hz, 2H, ArH), 8.53 (s, 1H, -N=CH),
9.66 (bs, 1H, NH). 13C NMR (DMSO-d6 100 MHz) δ: 6.5
(cyclopropane C), 9.2 (cyclopropane C), 56.65 (CH3, -OCH3),
Cyclopentanecarboxylic acid [4-(6,7-dimethoxy-
quinazolin-4-ylamino)phenyl]-[(E)-hydroxyiminomethyl]-
amide (7j): Starting from 0.16 g of cyclopentane carboxylic
acid (j) the title compound 7j was obtainedYellow solid;Yield:
0.46 g (73 %); m.p.: 185-186 °C; IR (ATR, νmax, cm-1): 3213.98