S. H. Yang et al. / Bioorg. Med. Chem. 19 (2011) 968–977
975
aromatic-H), 4.00 (3H, s, –OCH3), 3.99 (3H, s, –OCH3), 2.21 (3H, s, –
low solid (55 mg, 41%). 1H NMR (300 MHz, DMSO-d6) d: 10.95
(1H, s, NH), 8.55 (1H, s, –N@CH), 8.04 (1H, s, aromatic-H), 7.32
(1H, s, aromatic-H), 3.97 (6H, s, –2OCH3), 3.96–3.87 (6H, m, N–
CH2–CH2–), 2.79 (3H, s, –CH3), 2.78–2.73 (2H, m, N–CH2–CH2–).
ESI-MS: m/z (304, MH+).
CH3). ESI-MS: m/z (330, MHꢀ).
4.1.8. (6,7-Dimethoxyquinazolin-4-yl)-p-tolylamine
hydrochloride (5f)
Compound 3 (90 mg, 0.40 mmol) and 4-methylaniline (52 mg,
0.48 mmol) in 2-propanol gave product 5f as a light green solid
(80 mg, 60%). 1H NMR (300 MHz, DMSO-d6) d: 11.23 (1H, s, NH),
8.79 (1H, s, –N@CH), 8.22 (1H, s, aromatic-H), 7.54 (2H, d,
J = 8.4 Hz, aromatic-H), 7.31 (1H, s, aromatic-H), 7.30 (2H, d,
J = 8.1 Hz, aromatic-H), 4.00 (3H, s, –OCH3), 3.99 (3H, s, –OCH3),
2.36 (3H, s, –CH3). ESI-MS: m/z (330, MHꢀ).
4.1.15. (6,7-Dimethoxyquinazolin-4-yl)-(2-morpholin-4-
ylethyl)amine hydrochloride (5m)
Compound 3 (100 mg, 0.44 mmol) and 4-(2-aminoethyl)-mor-
pholine (88 mg, 0.67 mmol) in 2-propanol gave product 5m as a
beige solid (114 mg, 73%). 1H NMR (300 MHz, CDCl3) d: 8.56 (1H,
s, –N@CH), 7.21 (1H, s, aromatic-H), 6.92 (1H, s, aromatic-H),
4.02 (3H, s, –OCH3), 4.01 (3H, s, –OCH3), 3.76 (4H, t, J = 4.5 Hz,
O–CH2–CH2–), 3.71 (2H, t, J = 4.7 Hz, aliphatic-H), 2.76 (2H, t,
J = 5.9 Hz, aliphatic-H), 2.59 (4H, t, J = 4.4 Hz, N–CH2–CH2–). ESI-
MS: m/z (319, MH+).
4.1.9. (2,3-Dichlorophenyl)-(6,7-dimethoxyquinazolin-4-
yl)amine hydrochloride (5g)
Compound
3 (80 mg, 0.35 mmol) and 2,3-dichloroaniline
(115 mg, 0.71 mmol) in 2-propanol gave product 5g as a white so-
lid (77 mg, 57%). 1H NMR (300 MHz, DMSO-d6) d: 11.61 (1H, s, NH),
8.82 (1H, s, aromatic-H), 8.24 (1H, s, aromatic-H), 7.75 (1H, dd,
J = 6.6, 2.4 Hz, aromatic-H), 7.71 (1H, s, aromatic-H), 7.56 (1H, dd,
J = 8.4, 2.4 Hz, aromatic-H), 7.35 (1H, s, aromatic-H), 4.01 (3H, s,
–OCH3), 4.00 (3H, s, –OCH3). ESI-MS: m/z (386, MH+).
4.1.16. (6,7-Dimethoxyquinazolin-4-yl)-(2-methoxyethyl)amine
hydrochloride (5n)
Compound 3 (80 mg, 0.35 mmol) and 2-methoxyethylamine
(54 mg, 0.71 mmol) in 2-propanol gave product 5n as a brown so-
lid (29 mg, 28%) after re-crystallization with 2-propanol. 1H NMR
(300 MHz, DMSO-d6) d: 9.73 (1H, s, NH), 8.75 (1H, s, –N@CH),
7.95 (1H, s, aromatic-H), 7.21 (1H, s, aromatic-H), 3.95 (3H, s, –
OCH3), 3.94 (3H, s, –OCH3), 3.85 (2H, dd, J = 10.9, 5.2 Hz, ali-
phatic-H), 3.62 (2H, t, J = 5.4 Hz, aliphatic-H), 3.29 (3H, s, –CH3).
ESI-MS: m/z (264, MH+).
4.1.10. 4-(6,7-Dimethoxyquinazolin-4-ylamino)benzonitrile
hydrochloride (5h)
Compound 3 (80 mg, 0.35 mmol) and 4-cyanoaniline (86 mg,
0.71 mmol) in 2-propanol gave product 5h as a white solid
(79 mg, 66%). 1H NMR (300 MHz, DMSO-d6) d: 11.21 (1H, s, NH),
8.90 (1H, s, –N@CH), 8.23 (1H, s, aromatic-H), 8.02 (2H, d,
J = 8.4 Hz, aromatic-H), 7.95 (2H, d, J = 8.7 Hz, aromatic-H), 7.32
(1H, s, aromatic-H), 4.03 (3H, s, –OCH3), 4.01 (3H, s, –OCH3). ESI-
MS: m/z (341, MHꢀ).
4.1.17. [2-(3,4-Dimethoxyphenyl)ethyl]-(6,7-
dimethoxyquinazolin-4-yl)-amine Hydrochloride (5o)
Compound 3 (100 mg, 0.44 mmol) and 3,4-dimethoxypheneth-
ylamine (125 mg, 0.67 mmol) in 2-propanol gave product 5o as a
brown solid (115 mg, 64%) after re-crystallization with 2-propanol.
1H NMR (300 MHz, DMSO-d6) d: 8.36 (1H, s, –N@CH), 7.59 (1H, s,
aromatic-H), 7.08 (1H, s, aromatic-H), 6.76 (3H, t, J = 7.9 Hz, aro-
matic-H), 3.89 (3H, s, –OCH3), 3.87 (3H, s, –OCH3), 3.74 (3H, s, –
OCH3), 3.72 (3H, s, –OCH3), 2.94 (2H, t, J = 7.5 Hz, aliphatic-H),
2.74 (2H, t, J = 7.1 Hz, aliphatic-H). ESI-MS: m/z (406, MH+).
4.1.11. 5-(6,7-Dimethoxyquinazolin-4-ylamino)-2-
methylbenzonitrile hydrochloride (5i)
Compound 3 (80 mg, 0.35 mmol) and 3-cyano-4-methylaniline
(97 mg, 0.71 mmol) in 2-propanol gave product 5i as a white solid
(86 mg, 69%). 1H NMR (300 MHz, DMSO-d6) d: 11.28 (1H, s, NH),
8.88 (1H, s, –N@CH), 8.21 (1H, s, aromatic-H), 8.17 (1H, s, aro-
matic-H), 7.92 (1H, d, J = 8.4 Hz, aromatic-H), 7.59 (1H, d,
J = 8.4 Hz, aromatic-H), 7.30 (1H, s, aromatic-H), 4.02 (3H, s, –
OCH3), 4.01 (3H, s, –OCH3), 2.53 (3H, s, –CH3). ESI-MS: m/z (357,
MH+).
4.1.18. (6,7-Dimethoxyquinazolin-4-yl)naphthalen-1-ylamine
hydrochloride (5p)
Compound 3 (80 mg, 0.35 mmol) and 1-aminonaphthalene
(102 mg, 0.71 mmol) in 2-propanol gave product 5p as a purple so-
lid (92 mg, 71%). 1H NMR (300 MHz, DMSO-d6) d: 11.62 (1H, s, NH),
8.66 (1H, s, –N@CH), 8.30 (1H, s, aromatic-H), 8.06 (2H, t, J = 6.9 Hz,
aromatic-H), 7.89 (1H, d, J = 7.8 Hz, aromatic-H), 7.69–7.64 (2H, m,
aromatic-H), 7.62–7.53 (2H, m, aromatic-H), 7.31 (1H, s, –OCH3),
4.06 (6H, s, –2OCH3). ESI-MS: m/z (368, MH+).
4.1.12. (4-Bromophenyl)-(6,7-dimethoxyquinazolin-4-yl)amine
hydrochloride (5j)
Compound 3 (80 mg, 0.35 mmol) and 4-bromoaniline (48 mg,
0.43 mmol) in DMF afforded product 5j as a white solid (70 mg,
57%). 1H NMR (300 MHz, DMSO-d6) d: 11.19 (1H, s, NH), 8.83
(1H, s, –N@CH), 8.21 (1H, s, aromatic-H), 7.69 (4H, s, aromatic-
H), 7.30 (1H, s, aromatic-H), 4.01 (3H, s, –OCH3), 4.00 (3H, s, –
OCH3). ESI-MS: m/z (394, MHꢀ).
4.1.19. (4-Chlorobenzothiazol-2-yl)-(6,7-dimethoxyquinazolin-
4-yl)amine hydrochloride (5q)
Compound 3 (80 mg, 0.35 mmol) and 2-amino-4-chlorobenzo-
thiazole (102 mg, 0.71 mmol) in 2-propanol gave product 5q as a
green solid (16 mg, 9%) after re-crystallization with 2-propanol.
1H NMR (300 MHz, DMSO-d6) d: 9.08 (1H, s, –N@CH), 8.35 (1H, s,
aromatic-H), 8.03–7.98 (1H, m, aromatic-H), 7.57 (1H, d,
J = 7.8 Hz, aromatic-H), 7.40 (1H, s, aromatic-H), 7.31–7.28 (1H,
m, aromatic-H), 4.00 (6H, s, –2OCH3). ESI-MS: m/z (409, MH+).
4.1.13. (6,7-Dimethoxyquinazolin-4-yl)morpholin-4-ylamine
hydrochloride (5k)
Compound 3 (100 mg, 0.44 mmol) and 1-aminomorpholine
(92 mg, 0.89 mmol) in 2-propanol gave product 5k as a yellow so-
lid (42 mg, 29%). 1H NMR (300 MHz, DMSO-d6) d: 8.41 (1H, s, –
N@CH), 7.93 (1H, s, aromatic-H), 7.20 (1H, s, aromatic-H), 3.93
(6H, s, –2OCH3), 3.79–3.76 (2H, m, N–CH2–CH2–), 3.70–3.66 (2H,
m, N–CH–CH2–), 2.99 (2H, m, O–CH2–CH2–), 2.90 (2H, m, O–
CH2–CH2–). ESI-MS: m/z (327, MH+).
4.1.20. (6,7-Dimethoxyquinazolin-4-yl)pyridin-2-
ylmethylamine (5r)
Compound 3 (100 mg, 0.44 mmol) and 2-aminomethylpyridine
(243 mg, 2.22 mmol) in dioxane gave product 5r as a beige solid
(55 mg, 42%) through column purification. 1H NMR (300 MHz,
DMSO-d6) d: 8.63 (1H, d, J = 4.6 Hz, –N@CH–CH2), 8.59 (1H, s, –
N@CH–N), 7.72 (1H, t, J = 7.7 Hz, aromatic-H), 7.40 (1H, d,
4.1.14. (6,7-Dimethoxyquinazolin-4-yl)-(4-methylpiperazin-1-
yl)amine (5l)
Compound 3 (100 mg, 0.44 mmol) and 1-amino-4-mehtylpiper-
azine (79 mg, 0.67 mmol) in 2-propanol gave product 5l as a yel-