T. N. Le et al. / Bioorg. Med. Chem. 19 (2011) 4399–4404
4403
for 24 h. The reaction was quenched with water and extracted with
methylene chloride. The methylene chloride solution was sequen-
tially washed with 5% aqueous NaOH, water, and brine and dried
over anhydrous sodium sulfate. After removing the solvent, the
residue was separated by column chromatography on silica gel
with methylene chloride–methanol (20:1) to give the desired com-
pound. Treatment of the free amine compound with cHCl in ace-
tone gave the hydrochloride salt form of the amines as precipitates.
1H), 4.41 (m, 1H), 2.25 (m, 2H), 1.87–1.31 (m, 8H). Anal.
(C20H21N) C, H, N. EIMS m/z (%): 303 (M+, 10).
5.2.9. 3-(2-Phenylquinazolin-4-ylamino)propionic acid ethyl
ester (7i)
Oil (88%). mp: 268–270 °C (HCl salt). IR (cmꢀ1): 3402, 1728,
1571, 1531. 1H NMR (300 MHz, CDCl3) d: 8.57–8.53 (m, 2H); 7.91
(m, 1H); 7.73–7.68 (m, 2H); 7.49–7.39 (m, 4H); 6.51 (t, J = 5.7 Hz,
1H); 4.15 (q, J = 6 Hz, 2H); 4.09 (q, J = 7.2 Hz, 2H); 2.81 (t,
J = 6 Hz, 2H); 1.25 (t, J = 7.2 Hz, 3H). HRMS-EI (Calcd for C18 H17
N3O2): 307.3551. Found: 307.3556. EIMS m/z (%): 307 (M+, 65).
5.2.1. 4-(4-Methylpiperazin-1-yl)-2-phenylquinazoline (7a)
White solid (88%). mp: 92.5–93.5 °C, 270–272 °C (HCl salt). IR
(cmꢀ1): 2963, 1557, 1500. 1H NMR (300 MHz, CDCl3) d: 8.55 (m,
2H), 7.97 (m, 1H), 7.95 (m, 1H), 7.72 (m, 1H), 7.49–7.40 (m, 4H),
3.90 (t, J = 5 Hz, 4H), 2.67 (t, J = 5 Hz, 4H), 2.39 (s, 3H). Anal.
(C19H20N4) C, H, N. EIMS m/z (%): 304 (M+, 3).
5.2.10. Methyl(2-phenylquinazolin-4-yl)amine (7j)
White solid (81%). mp: 94–96 °C, 297–299 °C (HCl salt). IR
(cmꢀ1): 3340, 2956, 1570, 1527. 1H NMR (300 MHz, CDCl3) d:
8.60–8.56 (m, 2H), 7.90 (m, 2H), 7.69–7.63 (m, 1H), 7.49–7.34
(m, 4H), 5.83 (d, J = 4.2 Hz, 1H), 3.28 (d, J = 4.2 Hz, 2H). Anal.
(C15H13N3) C, H, N. EIMS m/z (%): 235 (M+, 48).
5.2.2. 4-Morpholin-4-yl-2-phenylquinazoline (7b)
White solid (94%), IR (cmꢀ1): 2968, 1560, 1500. mp: 124–
125 °C, 291–293 °C (HCl salt). 1H NMR (300 MHz, CDCl3) d: 8.57–
8.54 (m, 2H), 7.98 (m, 1H), 7.88 (m, 1H), 7.73 (m, 1H), 7.50–7.42
(m, 4H), 3.96–3.93 (m, 4H), 3.87–3.83 (m, 4H). Anal. (C18H17N3O)
C, H, N. EIMS m/z (%): 291 (M+, 39).
5.2.11. N,N,N0-Trimethyl-N0-(2-phenylquinazolin-4-yl)ethane-
1,2-diamine (7l)
Oil (91%). mp: 286–288 °C (HCl salt). IR (cmꢀ1): 2963, 1557,
1500. 1H NMR (300 MHz, CDCl3) d: 8.56–8.52 (m, 2H), 8.01 (m,
1H), 7.92 (m, 1H), 7.68 (m, 1H), 7.48–7.34 (m, 4H), 3.94 (t,
J = 8 Hz, 2H), 3.46 (s, 3H), 2.79 (d, J = 8 Hz, 2H), 2.34 (s, 6H).
HRMS-EI (Calcd for C19 H22 N4): 306.4139. Found: 306.4135. EIMS
m/z (%): 306 (M+, 28).
5.2.3. (2-Methoxyethyl)-(2-phenylquinazolin-4-yl)amine (7c)
Yellow solid (90%). mp: 130.5–131.5 °C, 228–230 °C (HCl salt).
IR (cmꢀ1): 3355, 2978, 1570, 1533. 1H NMR (300 MHz, CDCl3) d:
8.57–8.53 (m, 2H), 7.92 (m, 1H), 7.73–7.68 (m, 2H), 7.50–7.37
(m, 4H), 6.14 (t, J = 4.7 Hz, 1H), 4.01 (q, J = 5.1 Hz, 2H), 3.73 (t,
J = 5.1 Hz, 2H), 3.44 (s, 3H). Anal. (C17H17N3O) C, H, N. EIMS m/z
(%): 279 (M+, 85).
Acknowledgment
This work was supported by Korea Research Foundation grant
(KRF-2009-0071379).
5.2.4. 4-(4-Methyl-[1,4]diazepan-1-yl)-2-phenylquinazoline
(7d)
White solid (88%). mp: 81–83 °C. IR (cmꢀ1): 2962, 1557, 1500.
1H NMR (300 MHz, CDCl3) d: 8.57–8.52 (m, 2H), 7.97–7.91 (m,
2H), 7.68 (m, 2H), 7.50–7.38 (m, 4H), 4.19 (m, 2H), 4.09 (t,
J = 5 Hz, 2H), 3.00 (m, 2H), 2.68 (m, 2H), 2.42 (s, 3H), 2.23 (m,
2H). Anal. (C20H22N4) C, H, N. EIMS m/z (%): 318 (M+, 40).
References and notes
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Biochem. 1989, 58, 351.
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M. A.; Benedetti, P.; Viglianti, G. A.; Wang, J. C. Cancer Res. 1989, 49, 6318; (c)
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5.2.5. (2-Phenylquinazolin-4-ylamino)acetic acid methyl ester
(7e)
White solid (85%). mp: 140–141 °C, 235–237 °C (HCl salt). IR
(cmꢀ1): 1342, 1728, 1571, 1531. 1H NMR (300 MHz, CDCl3) d:
8.57–8.54 (m, 2H), 7.92 (m, 1H), 7.81–7.70 (m, 2H), 7.49–7.40
(m, 4H), 6.49 (t, J = 4.8 Hz, 1H), 4.52 (d, J = 4.8 Hz, 2H), 3.84 (s,
3H). EIMS m/z (%): 293 (M+, 44).
6. Yamashita, Y.; Fujii, N.; Murakaya, C.; Ashizawa, T.; Okabe, M.; Nakano, H.
Biochemistry 1992, 31, 12069.
5.2.6. Benzyl(2-phenylquinazolin-4-yl)amine (7f)
White solid (84%). mp: 121.5–123.5 °C, 272–274 °C (HCl). IR
(cmꢀ1): 3300, 1561, 1530. 1H NMR (300 MHz, CDCl3) d: 8.59–
8.55 (m, 2H), 7.93 (m, 1H), 7.73–7.70 (m, 2H), 7.48–7.37 (m, 9H),
5.96 (t, 1H), 5.02 (t, J = 5.4 Hz, 2H). Anal. (C21H17N3) C, H, N. EIMS
m/z (%): 311 (M+, 78).
7. Yamashita, Y.; Kawada, S.; Fujii, N.; Nakano, H. Biochemistry 1991, 30, 5838.
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5.2.7. Isopropyl(2-phenylquinazolin-4-yl)amine (7g)
Yellow solid (89%). mp: 147–148 °C, 280–282 °C (HCl salt). IR
(cmꢀ1): 3285, 2964, 1566, 1524. 1H NMR (300 MHz, CDCl3) d:
8.58–8.55 (m, 2H), 7.90 (m, 1H), 7.73–7.66 (m, 2H), 7.49–7.42
(m, 4H), 5.48 (d, 1H), 4.73 (m, 1H), 1.41 (d, J = 5 Hz, 6H). Anal.
(C17H17N3) C, H, N. EIMS m/z (%): 263 (M+, 36).
5.2.8. Cyclohexyl(2-phenylquinazolin-4-yl)amine (7h)
White solid (84%). mp: 154–155 °C, 262–264 °C. IR (cmꢀ1):
3300, 1561, 1530. 1H NMR (300 MHz, CDCl3) d: 8.56–8.53 (m,
2H), 7.90 (m, 1H), 7.72–7.65 (m, 2H), 7.49–7.39 (m, 4H), 5.54 (d,