2928
S. Tu et al. / Bioorg. Med. Chem. Lett. 16 (2006) 2925–2928
˚
a = 10.3031(16), b = 10.7991(17), c = 17.207(3) A, a = c =
Province Open Foundation (No. KJS02060) for finan-
cial support.
3
˚
90ꢁ, b = 101.942(3)ꢁ, V = 1873.1(5) A , Mr = 355.44, Z = 4,
Dc = 1.260 g/cm , k = 0.71073 A, l(Moka) = 0.087 mm
F(000) = 760, R1 = 0.0447, wR2 = 0.1011.
3
À1
,
˚
References and notes
16. The general procedure is represented below: All reactions
were performed in a monomodal EmrysTM Creator from
1. (a) Abd, E.; Hisham, A. Pharmazie 1997, 52, 28; (b) Sun,
H. B.; Qing, F. L.; Chen, X. F. Synthesis 1997, 1249; (c)
Nevile, C. F.; Grundon, M. F.; Ramchandran, V. N.;
Reisch, G.; Reisch, J. J. Chem. Soc. Perkin Trans. 1 1991,
2261; (d) Reil, E.; Scoll, M.; Masson, K.; Oettmeier, W.
Biochem. Soc. Trans. 1994, 22, 62; (e) Mandi, Y.; Regely,
K.; Ocsovszky, I.; Barbe, J.; Galy, J. P.; Molnar, J.
Anticancer Res. 1994, 14, 2633.
2. (a) Sit, S.-Y.; Meanwell, N. A. U.S. 5,892,045, April 6,
1999; (b) Hewawasam, P.; Starrett, J. E., Jr.; Swartz, S. G.
U.S. 5,972,961, October 26, 1999; (c) Hewawasam, P.;
Starrett, J. E., Jr. U.S. 6,184,231, February 6, 2001.
3. (a) Doherty, J. B.; Stelmach, J. E.; Chen, M. -H.; Liu, L.;
Hunt, J. A.; Ruzek, R. D.; Goulet, J. L.; Wisnoski, D. D.;
Natarajan, S. R.; Rupprecht, K. M.; Bao, J.; Miao, S.;
Hong, X. WO 0258695, 2002; (b) Dahlen, E.; Andersson,
M.; Dawe, K.; Tellander, A. C.; Brunmark, C.; Bjork, A.;
Hedlung, G. Autoimmunity 2000, 32, 198; (c) Sada, Y.;
Adegawa, S.; Mogi, K.; Honda, H.; Eto, H.; Morimoto,
S.; Okawa, J.; Umehara, N.; Sato, S. JP 97-234547, 1999;
(d) Shibutani, N.; Hashimoto, K.; Inoue, Y.; Sato, K.;
Miki, S. JP 97-183870, 1999; (e) End, D. W.; Venet, M. G.;
Angibaud, P. R.; Sanz, G. C. WO 96-EP4661, 1997; (f)
Afonso, A.; Weinstein, J.; Gentles, M.J. WO 91-US6251,
1995.
4. Suarez, M.; Ochoa, E.; Verdecia, Y.; Pita, B.; Moran, L.;
Martin, N.; Quinteiro, M.; Seoane, C.; Soto, J. L.; Novoa,
H.; Blaton, N.; Peters, O. M. Tetrahedron 1999, 55, 875.
5. Tu, S. J.; Wei, Q. H.; Ma, H. J.; Shi, D. Q.; Gao, Y.; Cui,
G. Y. Synth. Commun. 2001, 31, 2657.
6. Strozher, F. M.; Lieldriedis, F. I. Khim. Geterotsikl.
Soedin. 1993, 9, 1227.
7. Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl.
1993, 32, 131.
8. Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown,
S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123.
9. (a) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. Engl.
2000, 39, 3168; (b) Bienayme, H.; Hulme, C.; Oddon, G.;
Schmitt, P. Chem. Eur. J. 2000, 6, 3321.
10. (a) Bose, A. K.; Banik, B. K.; Lavlinskaia, N.; Jayaraman,
M.; Manhas, M. S. Chemtech. 1997, 27, 18; (b) Caddick, S.
Tetrahedron 1995, 51, 10403.
11. Gedye, R.; Smith, F.; Westawaym, K.; Humera, A.;
Baldisern, L.; Laberge, L.; Rousell, J. Tetrahedron Lett.
1986, 27, 279.
12. All microwave reactions were performed on an Emrys
Optimizer (Personal Chemistry, Available from: <http://
Personal Chemistry, Uppsala, Sweden. In a 10 mL
EmrysTM reaction vial, aldehyde (2 mmol), Meldrum’s
acid (2 mmol), dimedone (2 mmol), and amine (2 mmol) in
95% ethanol (5 mL) were mixed and then capped. The
mixture was irradiated for 4–9 min at 200 W power and
100 ꢁC. The reaction mixture was cooled to room
temperature and the solid product was filtered, and then
washed with ether. It was recrystallized by DMF and dried
to give the pure product. All products are characterized by
IR and 1H NMR spectral data. Spectra of five compounds
are summarized as follows:
Compound 5a. Mp: 175.4–176.0 ꢁC; IR(KBr,m,cmÀ1):
2962, 2896, 1690, 1619, 1487, 1459, 1301, 1198, 1107, 838;
1H NMR (DMSO-d6) (d, ppm): 7.31 (d, 2H, J = 8.4 Hz,
ArH), 7.12 (d, 2H, J = 8.4 Hz, ArH), 4.17 (t, 1H,
J = 7.2 Hz, CH), 3.13 (s, 3H, NCH3), 2.96 (dd, 1H,
J = 16.0 Hz, J = 7.6 Hz, NCOCH2), 2.84 (dd, 1H,
J = 17.6 Hz, J = 8.0 Hz, NCOCH2), 2.62 (d, 1H,
8
8
J = 16.0 Hz, CH2), 2.53 (d, 1H, J = 16.4 Hz, CH2), 2.29
(d, 1H, J = 16.0 Hz, COCH2), 2.17 (d, 1H, J = 16.0 Hz,
COCH2), 1.09 (s, 3H, CH3), 1.07 (s, 3H, CH3).
Compound 5k. Mp: 154.1–155.0 ꢁC; IR(KBr,m,cmÀ1):
3041, 2977, 1772, 1656, 1601, 1541, 1507, 1463, 805; 1H
NMR (DMSO-d6) (d, ppm): 7.08 (d, 2H, J = 8.4 Hz, ArH),
7.06 (d, 2H, J = 8.4 Hz, ArH), 4.10 (t, 1H, J = 6.4 Hz, CH),
3.06 (dd, 1H, J = 16.0 Hz, J = 4.4 Hz, NCOCH2), 2.87 (dd,
1H, J = 16.4 Hz, J = 6.8 Hz, NCOCH2), 2.75 (d, 1H,
8
8
J = 16.0 Hz, CH2), 2.70 (d, 1H, J = 16.0 Hz, CH2), 2.57
(d, 1H, J = 16.8 Hz, COCH2), 2.41 (d, 1H, J = 16.0 Hz,
COCH2), 2.35–2.30 (m, 1H, NCH), 2.06–2.01 (m, 2H,
7CH2), 0.98–0.91 (m, 2H, CH2), 0.61–0.30 (m, 2H, CH2).
Compound 5m. Mp: 157.9–158.5 ꢁC; IR(KBr,m,cmÀ1):
1
2960, 2926, 1684, 1646, 1490, 1408, 1366, 844; H NMR
(DMSO-d6) (d, ppm): 7.45 (d, 2H, J = 8.8 Hz, ArH), 7.08
(d, 2H, J = 8.4 Hz, ArH), 4.19 (t, 1H, J = 8.0 Hz, CH),
4.15–4.09 (m, 1H, NCH), 2.99 (dd, 1H, J = 16.0 Hz,
J = 7.2 Hz, NCOCH2), 2.91 (dd, 1H, J = 16.4 Hz,
J = 7.2 Hz, NCOCH2), 2.52 (d, 1H, J = 11.6 Hz, 8CH2),
8
2.39 (d, 1H, J = 16.4 Hz, CH2), 2.35 (d, 1H, J = 17.2 Hz,
COCH2), 2.14 (d, 1H, J = 16.0 Hz, COCH2), 1.79–1.47 (m,
8H, 4· CH2), 1.13 (s, 3H, CH3), 1.04 (s, 3H, CH3).
Compound 5q. Mp: 163.0–164.1 ꢁC; IR(KBr,m,cmÀ1):
2931, 2850, 1692, 1616, 1486, 1346, 1287, 1086, 982, 840;
1H NMR (DMSO-d6) (d, ppm): 7.43 (d, 2H, J = 8.4 Hz,
ArH), 7.13 (d, 2H, J = 8.4 Hz, ArH), 4.49 (t, 1H, J = 8.0 Hz,
CH), 4.12–4.04 (m, 1H, NCH), 2.97 (dd, 1H, J = 16.8 Hz,
J = 7.2 Hz, NCOCH2), 2.87 (dd, 1H, J = 16.0 Hz,
J = 7.2 Hz, NCOCH2), 2.51 (d, 1H, J = 5.6 Hz, 8CH2),
8
13. Tu, S. J.; Zhu, X. T.; Zhang, J. P.; Xu, J. N.; Wang, Q.
Acta Crystallogr. 2005, E61, o3536.
14. Tu, S. J.; Zhu, X. T.; Zhang, J. P.; Xu, J. N.; Wang, Q.
Acta Crystallogr. 2005, E61, o4372.
2.49 (d, 1H, J = 7.2 Hz, CH2), 2.36 (d, 1H, J = 16.0 Hz,
COCH2), 2.26 (d, 1H, J = 16.8 Hz, COCH2), 2.22–2.18 (m,
10H, 5· CH2), 1.12 (s, 3H, CH3), 1.04 (s, 3H, CH3).
Compound 5r. Mp: 206.1–207.2 ꢁC; IR(KBr, m, cmÀ1):
2964, 2872, 1715, 1645, 1622, 1510, 1373, 1265, 1191, 1094,
781, 759; 1H NMR (DMSO-d6) (d, ppm): 7.57 (d, 1H,
J = 8.4 Hz, ArH), 7.42–7.32 (m, 3H, ArH), 7.23 (dd, 2H,
J = 21.6 Hz, J = 6.8 Hz, ArH), 7.03 (d, 1H, J = 7.2 Hz,
ArH), 4.58 (t, 1H, J = 7.6 Hz, CH), 3.33 (dd, 1H, J =
13.2 Hz, J = 3.6 Hz, NCOCH2), 2.59 (dd, 1H, J = 16.0 Hz,
J = 4.0 Hz, NCOCH2), 2.51 (dd, 1H, J = 16.0 Hz,
J = 5.6 Hz, 8CH2), 2.43 (dd, 1H, J = 17.6 Hz,
J = 6.8 Hz,8CH2), 2.38 (s, 3H, Ar-CH3), 2.15 (d, 1H,
J = 16.0 Hz, COCH2), 1.99 (d, 1H, J = 17.6 Hz, COCH2),
1.01 (s, 3H, CH3), 0.98 (s, 3H, CH3).
15. The single-crystal growth was carried out in ethanol at room
temperature. X-ray crystallographic analysis was per-
formed with a Siemens SMART CCD and a Semens P4
diffractometer. Crystal data for 5a: C18H20ClNO2, yellow,
crystal dimension 0.29 · 0.25 · 0.17 mm, orthorhombic,
space group Pca2(1), a = 17.492(3), b = 9.805(2), c =
3
˚
˚
9.634(2) A, a = b = c = 90ꢁ, V = 1652.3(7) A , Mr = 317.80,
Z = 4, Dc = 1.278 g/cm3, k = 0.71073 A, l(Moka) =
˚
0.238 mmÀ1, F(000) = 672, R1 = 0.0591, wR2 = 0.1491.
Crystal data for 5o: C22H26FNO2, yellow, crystal dimension
0.28 · 0.26 · 0.24 mm, monoclinic, space group P2(1)/n,