1428
Z. Wei, L. Zheng, Q. Dang, and X. Bai
Vol 46
2H), 7.84–7.77 (m, 2H), 7.55–7.48 (m, 2H). 13C NMR (75
MHz, DMSO-d6): d ¼ 162.2, 158.2, 150.6, 150.2, 149.2,
135.0, 133.8, 133.1, 127.7, 125.6, 123.7, 123.4, and 113.4. ES-
MS: m/z 223 [M þ Hþ].
(m, 1H). 13C NMR (75 MHz, DMSO-d6): d ¼ 170.0, 161.9,
150.2, 132.4, 131.5, 128.8, 128.6, 127.1, 124.3, 123.4, 113.0,
47.0, 31.4, and 25.9. ES-MS: m/z 366 [M þ Hþ].
Benzyl (4-aminoquinazolin-2-yl)methylcarbamate (6g).
White solid, mp 209ꢀC (decomp.); 1H NMR (300 MHz,
DMSO-d6): d ¼ 8.19 (d, J ¼ 8.4 Hz, 1H), 7.77–7.72 (m, 3H),
7.63 (d, J ¼ 8.1 Hz, 1H), 7.50–7.35 (m, 6H), 5.07 (s, 2H),
4.22 (d, J ¼ 6.0 Hz, 2H). 13C NMR (75 MHz, DMSO-d6): d
¼ 163.1, 162.0, 156.3, 149.8, 137.3, 132.8, 128.3, 127.7,
127.6, 127.0, 124.9, 123.6, 113.3, 65.2, and 46.5. ES-MS: m/z
309 [M þ Hþ].
4-Amino-2-(quinolin-2-yl)quinazoline (5h). White solid,
1
mp 261–262ꢀC; H NMR (300 MHz, DMSO-d6): d ¼ 8.59 (d,
J ¼ 9.0 Hz, 1H), 8.49 (d, J ¼ 8.1 Hz, 1H), 8.31 (d, J ¼ 8.1
Hz, 1H), 8.16 (d, J ¼ 9.0 Hz, 1H), 8.07 (br. 2H), 8.04 (s, 1H),
7.90–7.80 (m, 3H), 7.66 (t, J ¼ 7.5 Hz, 1H), 7.56 (t, J ¼ 7.2
Hz, 1H). 13C NMR (75 MHz, DMSO-d6): d ¼ 162.6, 160.0,
156.2, 150.2, 147.4, 136.3, 133.1, 129.7, 129.5, 128.0, 127.9,
127.8, 127.1, 126.0, 123.6, 121.1, and 113.6. ES-MS: m/z 273
[M þ Hþ].
Benzyl
3-amino-1-(4-amino-6-chloroquinazolin-2-yl)-3-
oxopropylcarbamate (7a). Yellow solid, mp 252–254ꢀC;
[a]1D5¼ ꢂ92.2 (c ¼ 1, MeOH:TFA ¼ 10:1); 1H NMR (300
MHz, DMSO-d6): d ¼ 8.34 (d, J ¼ 2.4 Hz, 1H), 7.82 (br.,
2H), 7.74 (dd, J ¼ 2.1 Hz, 8.7 Hz, 1H), 7.60 (d, J ¼ 9.0 Hz,
1H), 7.40 (d, J ¼ 8.4 Hz, 1H), 7.27 (s, 5H), 7.24 (s, 1H), 7.03
(br, 1H), 5.03–4.96 (t, 2H), 4.62–4.60 (t, 1H), 3.32–3.09 (t,
1H), 3.97–3.92 (t, 1H). 13C NMR (75 MHz, DMSO-d6): d ¼
173.4, 164.2, 161.0, 155.7, 148.6, 137.0, 133.0, 129.2, 128.7,
128.2, 127.6, 127.4, 122.7, 113.7, 65.2, 53.4, and 40.9; ES-
MS: m/z 400 [M þ Hþ].
4-Amino-2-(furan-2-yl)quinazoline (5i). White solid, mp
221ꢀC (decomp.); 1H NMR (300 MHz, DMSO-d6): d ¼ 8.21
(d, J ¼ 8.1 Hz, 1H), 7.86–7.68 (m, 5H), 7.47–7.42 (m, 1H),
7.18 (d, J ¼ 2.7 Hz, 1H), 6.65 (t, J ¼ 1.5 Hz, 1H). 13C NMR
(75 MHz, DMSO-d6): d¼ 162.1, 153.7, 153.1, 150.2, 144.7,
133.2, 127.4, 125.1, 123.7, 113.4, 112.2, and 112.1. ES-MS:
m/z 212 [M þ Hþ].
4-Amino-2-methylquinazoline (6a). White solid, mp 226ꢀC
(decomp.); 1H NMR (300 MHz, DMSO-d6): d ¼ 8.47 (br.,
2H), 8.27 (d, J ¼ 8.7 Hz, 1H), 7.83 (t, J ¼ 7.5 Hz, 1H), 7.67
(d, J ¼ 8.1 Hz, 1H), 7.53 (t, J ¼ 7.5 Hz, 1H), 1.76 (s, 3H).
13C NMR (75 MHz, DMSO-d6): d ¼ 171.7, 162.8, 162.4,
134.1, 125.8, 124.2, 123.4, 111.9, and 24.2. ES-MS: m/z 160
[M þ Hþ].
4-amino-6-chloro-2-benzylquinazoline (7b). White solid,
1
mp 239–242ꢀC; H NMR (300 MHz, DMSO-d6): d ¼ 8.36 (d,
J ¼ 2.1 Hz, 1H), 8.19 (d, J ¼ 2.4 Hz, 1H), 8.03 (br., 2H),
7.35–7.25 (m, 5H), 7.21–7.18 (m, 1H), 4.02 (s, 2H). 13C NMR
(75 MHz, DMSO-d6): d ¼ 166.9, 161.7, 146.6, 138.7, 135.7,
128.9, 128.6, 128.2, 126.1, 123.6, 122.6, 114.2, and 45.6. ES-
MS: m/z 270 [M þ Hþ].
4-Amino-2-isopropylquinazoline (6b). White solid, mp
1
117–119ꢀC; H NMR (300 MHz, DMSO-d6): d ¼ 8.17 (d, J ¼
8.1 Hz, 1H), 7.74–7.68 (m, 3H), 7.61 (d, J ¼ 8.1 Hz, 1H),
7.43–7.38 (m ,1H), 2.95–2.90 (m, 1H), 1.26 (d, J ¼ 8.7 Hz,
6H). 13C NMR (75 MHz, DMSO-d6): d ¼ 170.8, 162.0, 150.1,
132.6, 127.0, 124.5, 123.4, 113.0, 37.1, and 21.7. ES-MS: m/z
188 [M þ Hþ].
Benzyl
3-amino-1-(4-amino-7-chloroquinazolin-2-yl)-3-
oxopropylcarbamate (7c). Yellow solid, mp 259–261ꢀC;
[a]1D5¼ ꢂ57.6 (c ¼ 1, MeOH:TFA ¼ 10:1); 1H NMR (300
MHz, DMSO-d6): d ¼ 8.22 (d, J ¼ 8.7 Hz, 1H), 7.88 (br.,
2H), 7.62 (d, J ¼ 1.8 Hz, 1H), 7.48 (dd, J ¼ 1.8 Hz, 8.7 Hz,
1H), 7.41 (d, J ¼ 8.4 Hz, 1H), 7.27 (s, 6H), 7.05 (s, 1H),
5.05–4.93 (m, 2H), 4.65–4.60 (m, 1H), 3.16–3.09 (m, 1H),
2.97–2.90 (m, 1H). 13C NMR (75 MHz, DMSO-d6): d ¼
173.5, 165.7, 165.0, 161.6, 155.7, 150.9, 137.3, 128.2, 127.6,
127.4, 125.7, 125.1, 111.5, 65.2, 53.6, and 40.9.; ES-MS: m/z
400 [M þ Hþ].
4-Amino-2-cyclohexylquinazoline (6c). White solid, mp
1
210–213ꢀC; H NMR (300 MHz, DMSO-d6): d ¼ 8.16 (d, J ¼
8.7 Hz, 1H), 7.72–7.55 (m, 4H), 3.39 (t, J ¼ 7.8 Hz, 1H),
2.64–2.56 (m, 1H), 1.92–1.55 (m, 7H), 1.41–1.21 (m, 3H). 13C
NMR (75 MHz, DMSO-d6): d ¼ 170.0, 162.0, 150.3, 132.4,
127.1, 124.4, 123.4, 113.0, 47.1, 31.4, and 25.9. ES-MS: m/z
228 [M þ Hþ].
4-Amino-7-chloro-2-benzylquinazoline (7d). White solid,
1
4-Amino-2-benzylquinazoline (6d). White solid, mp 240–
mp 210–212ꢀC; H NMR (300 MHz, DMSO-d6): d ¼ 8.20 (d,
1
242ꢀC; H NMR (300 MHz, DMSO-d6): d ¼ 8.16 (d, J ¼ 8.7
J ¼ 8.7 Hz, 1H), 7.90 (br., 2H), 7.68 (d, J ¼ 2.1 Hz, 1H),
7.49–7.46 (m, 1H), 7.36–7.16 (m, 5H), 3.98 (s, 2H). 13C NMR
(75 MHz, DMSO-d6): d ¼ 166.9, 162.0, 151.3, 139.0, 137.4,
128.9, 128.2, 127.7, 126.1, 125.7, 125.2, 111.4, and 45.5. ES-
MS: m/z 270 [M þ Hþ].
Hz, 1H), 7.75–7.69 (m, 3H), 7.65–7.62 (m, 1H), 7.44–7.39 (m,
1H), 7.34–7.24 (m, 4H), 7.20–7.15 (m, 1H), 3.99 (s, 2H). 13C
NMR (75 MHz, DMSO-d6): d ¼ 165.4, 162.1, 150.1, 139.3,
132.7, 128.9, 128.1, 127.0, 125.9, 124.7, 123.4, 112.7, and
45.6. ES-MS: m/z 236 [M þ Hþ].
4-Amino-2-(hydroxy(phenyl)methyl)quinazoline (6e). Yellow
oil; 1H NMR (300 MHz, CDCl3): d ¼ 7.89 (d, J ¼ 8.1 Hz,
1H), 7.79 (td, J ¼ 1.5, 6.6 Hz, 1H), 7.66 (d, J ¼ 8.1 Hz, 1H),
7.54–7.44 (m, 4H), 7.36–7.28 (m, 2H), 5.68 (br., 2H), 5.42
(br., 1H). 13C NMR (75 MHz, CDCl3): d ¼ 165.3, 161.8,
148.9, 142.7, 133.4, 128.4, 127.9, 127.8, 127.7, 126.0, 121.8,
113.3, and 75.1. ES-MS: m/z 252 [M þ Hþ].
Acknowledgments. This work was supported by grants
(20572032 and 90713008) from the National Natural Science
Foundation of China and Changchun Discovery Sciences.
REFERENCES AND NOTES
Benzyl 3-amino-1-(4-aminoquinazolin-2-yl)-3-oxopropyl-
carbamate (6f). White solid, mp 244–246ꢀC; [a]D15¼ ꢂ77.2 (c
¼ 1, MeOH:TFA ¼ 10:1); 1H NMR (300 MHz, DMSO-d6): d ¼
8.18 (d, J ¼ 8.1 Hz, 1H), 7.73 (t, J ¼ 6.9 Hz, 3H), 7.59 (d, J ¼
8.1 Hz, 1H), 7.45–7.43 (m, 2H), 7.26 (s, 5H), 7.05 (s, 1H), 5.04–
4.93 (m, 2H), 4.63–4.62 (m, 1H), 3.16–3.09 (m, 1H), 2.98–2.90
[1] Chen, J.; Stubbe, J. Nat Rev Cancer 2005, 5, 102.
[2] Rishel, M. J.; Hecht, S. M. Org Lett 2001, 3, 2867.
[3] Leitheiser, C. J.; Smith, K. L.; Rishel, M. J.; Hashimoto, S.;
Konishi, K.; Thomas, C. J.; Li, C.; McCormick, M. M.; Hecht, S. M. J
Am Chem. Soc 2003, 125, 8218.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet