1
032
Helvetica Chimica Acta – Vol. 98 (2015)
HÀC(8)); 6.86 (t, J ¼ 7.5, HÀC(6)); 7.30 – 7.34 (m, HÀC(7), 1 H of furan); 7.91 (dd, J ¼ 7.5, 1.3, HÀC(5)).
1
3
C-NMR: 38.6; 40.5; 52.4; 53.3; 75.2; 108.7; 110.6; 114.3; 119.5; 127.1; 128.6; 134.0; 141.8; 144.2; 150.8;
63.0; 168.5; 170.1. Anal. calc. for C H N O (358.12): C 60.33, H 5.06, N 7.82; found: C 60.50, H 4.84, N
1
18
18
2
6
7.69.
Methyl 3-Cyclopentyl-1,2,3,4-tetrahydro-2-(2-methoxy-2-oxoethyl)-4-oxoquinazoline-2-carboxylate
1
(
(
3
6
5f). White crystals. M.p. 93 – 958. IR: 3266, 3120, 3017, 2950, 1745, 1635, 1489. H-NMR: 1.48 – 1.56
m, CH ); 1.67 – 1.80 (m, CH ); 2.00 – 2.02 (m, CH ); 2.27 – 2.34 (m, CH ); 3.27 (d, J ¼ 16.1, CH , 1 H);
2
2
2
2
2
.27 (d, J ¼ 16.1, CH , 1 H); 3.40 (quint., J ¼ 8.0, NCH); 3.76 (s, MeO; 3.84 (s, MeO); 5.99 (br. s, NH);
2
.64 (d, J ¼ 7.9, HÀC(8)), 6.84 (t, J ¼ 7.9, HÀC(6)); 7.30 (td, J ¼ 7.9, 1.4, HÀC(7)); 7.83 (dd, J ¼ 7.9, 1.4,
13
HÀC(5)). C NMR: 23.8; 24.2; 29.0; 29.9; 40.1; 52.2; 53.5; 59.3; 78.0; 114.0; 119.5; 127.8; 132.6; 133.6;
1
6
43.5; 161.3; 170.2; 171.3. Anal. calc. for C H N O (346.15): C 62.42, H 6.40, N 8.09; found: C 62.28, H
18 22 2 5
.53, N 7.90.
Methyl 3-Cyclopropyl-1,2,3,4-tetrahydro-2-(2-methoxy-2-oxoethyl)-4-oxoquinazoline-2-carboxylate
1
(
5g). White crystals. M.p. 97 – 998. IR: 3294, 3141, 3056, 2950, 2864, 1735, 1623, 1489. H-NMR: 0.76 –
0
2
.79 (m, CH , 1 H); 0.82 – 0.87 (m, CH , 1 H); 0.89 – 0.95 (m, CH , 1 H); 1.00 – 1.06 (m, CH , 1 H);
2
2
2
2
.48 – 2.51 (m, NCH); 3.70 (d, J ¼ 16.0, CH , 1 H); 3.55 (d, J ¼ 16.0, CH , 1 H); 3.70 (s, MeO); 3.76 (s,
2
2
MeO); 6.70 (d, J ¼ 7.9, HÀC(8)); 6.84 (td, J ¼ 7.8, 1.0, HÀC(6)); 7.33 (td, J ¼ 7.8, 1.5, HÀC(7)); 7.90 (dd,
J ¼ 7.8, 1.5, HÀC(5)). Anal. calc. for C H N O (318.12): C 60.37, H 5.70, N 8.80; found: C, 60.15, H 5.91,
16
18
2
5
N 8.66.
Methyl 1,2,3,4-Tetrahydro-2-(2-methoxy-2-oxoethyl)-4-oxo-3-(propan-2-yl)quinazoline-2-carboxy-
1
late (5h). White crystals. M.p. 87 – 898. IR: 3284, 3135, 3044, 2953, 1742, 1635, 1538. H-NMR: (d, J ¼
6
.7, Me); 1.56 (d, J ¼ 6.7, Me); 3.00 (d, J ¼ 16.3, CH , 1 H); 3.31 – 3.34 (m, NCH, CH , 2 H); 3.75 (s,
2
2
MeO); 3.84 (s, MeO); 5.80 (br. s, NH); 6.63 (d, J ¼ 7.9, HÀC(8)); 6.84 (td, J ¼ 7.9, 1.0, HÀC(6)); 7.30 (td,
13
J ¼ 7.9, 1.0, HÀC(7)); 7.83 (dd, J ¼ 7.9, 1.0, HÀC(5)). C-NMR: 19.8; 21.0; 40.0; 50.6; 52.2; 53.4; 77.7;
1
6
14.0; 115.4; 119.5; 127.9; 133.6; 143.6; 161.8; 170.3; 171.4. Anal. calc. for C H N O (320.14): C 59.99, H
16 20 2 5
.29, N 8.74; found: C 60.14, H 6.41, N 8.51.
Methyl 1,2,3,4-Tetrahydro-2-(2-methoxy-2-oxoethyl)-4-oxo-3-(prop-2-en-1-yl)quinazoline-2-carbox-
1
ylate (5i). White crystals. M.p. 122 – 1248. IR: 3260, 3120, 3074, 3007, 2947, 1754, 1635. H-NMR: (d, J ¼
1
6.3, CH
2
, 1 H); 3.35 (d, J ¼ 16.3, CH
2
, 1 H); 3.74 (s, MeO; 3.84 (s, MeO); 4.05 (ddt, J ¼ 16.7, 5.1, 1.6,
NCH , 1 H); 4.37 (ddt, J ¼ 16.7, 5.1, 1.6, NCH , 1 H); 5.16 (dd, J ¼ 10.3, 1.4, ¼CH , 1 H); 5.20 (dd, J ¼ 17.2,
2
2
2
1
.4, ¼CH , 1 H); 5.87 (ddt, J ¼ 17.2, 10.3, 5.1, ¼CH, 1 H); 5.95 (br. s, NH); 6.68 (d, J ¼ 8.0, HÀC(8)); 6.85
2
13
(
td, J ¼ 8.0, 1.0, HÀC(6)); 7.31 (td, J ¼ 8.0, 1.5, HÀC(7)); 7.89 (dd, J ¼ 8.0, 1.5, HÀC(5)). C-NMR: 40.4;
4.8; 52.3; 53.2; 77.2; 114.2; 114.4; 116.4; 119.5; 128.5; 133.8; 133.9; 144.2; 162.4; 170.0; 170.9. Anal. calc.
for C H N O (318.12): C 60.37, H 5.70, N 8.80; found: C 60.51, H 5.58, N 8.67.
4
16
18
2
5
REFERENCES
[
[
[
[
1] A. Chanda, V. V. Fokin, Chem. Rev. 2009, 109, 725.
2] X.-Y. Liu, C.-M. Che, Angew. Chem., Int. Ed. 2008, 47, 3805.
3] C. I. Herrerías, X. Yao, Z. Li, C.-J. Li, Chem. Rev. 2007, 107, 2546.
4] S. Narayan, J. Muldoon, M. G. Finn, V. V. Fokin, H. C. Kolb, K. B. Sharpless, Angew. Chem., Int. Ed.
2
005, 44, 3275.
[
[
[
5] I. Khan, A. Ibrar, N. Abbas, A. Saeed, Eur. J. Med. Chem. 2014, 76, 193.
6] E. Cohen, B. Klarberg, J. R. Vaughan Jr., J. Am. Chem. Soc. 1960, 82, 2731.
7] B. Vijayakumar, C. P. Kumar, G. Sivaprasad, K. Nirosha, S. Rokkam, E. Mohanambal, Int. J. Novel
Trends Pharm. Sci. 2011, 1, 1.
[
[
8] G. M. S. da Silva, C. M. R SantꢁAnna, E. J. Barreiro, Bioorg. Med. Chem. 2004, 12, 3159.
9] X. Zhu, G. Zhao, X. Zhou, X. Xu, G. Xia, Z. Zheng, L. Wang, X. Yang, S. Li, Bioorg. Med. Chem.
Lett. 2010, 20, 299.
[
[
10] O. E. Sattarova, O. L. Vizgunova, É. V. Voronina, Pharm. Chem. J. 2006, 40, 73.
11] M. Tobe, Y. Isobe, H. Tomizawa, M. Matsumoto, F. Obara, T. Nagasaki, H. Hayashi, Bioorg. Med.
Chem. Lett. 2001, 11, 545.