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(d, J = 16.8 Hz, 1H), 4.84 (d, J = 16.8 Hz, 1H), 3.43 (m,
C16H18FN3O3ÆHCl: C, 54.01; H, 5.38; N, 11.81; Cl, 9.96.
Found: C, 54.11; H, 5.30; N, 11.74; Cl, 9.85. Compound
1H), 3.30 (m, 1H), 3.27 (dd, J = 17.2 and 5.6 Hz, 1H), 2.92
(m, 2H), 2.84 (dd, J = 17.2 and 4.8 Hz, 1H), 1.83 (m, 2H),
1.70 (m, 2H). 13C NMR: 203.4, 166.5, 163.3, 146.7, 134.2,
133.1, 128.9, 128.0, 126.9, 118.4, 80.7, 72.0, 63.3, 54.8,
51.2, 37.1, 31.4. Anal. Calcd for C17H18F3N3O3Æ1.5HCl:
C, 48.15; H, 4.64; N, 9.91. Found: C, 47.97; H, 4.60; N,
9.98. Compound 12 (hydrochloride salt): mp: 293–
25
17 (hydrochloride salt): mp: 276–277 ꢁC. ½aꢀD +15.4 (c
0.45, EtOH). 1H NMR: 8.17 (s, 1H), 7.81 (s, 1H), 7.62 (d,
J = 7.1 Hz, 1H), 7.47 (d, J = 7.1 Hz, 1H), 5.02 (d,
J = 16.7 Hz, 1H), 4.93 (d, J = 16.7 Hz, 1H), 3.45 (m,
1H), 3.29 (m, 1H), 3.21 (dd, J = 17.3 and 5.8 Hz, 1H), 2.80
(m, 2H), 2.74 (dd, J = 17.3 and 4.9 Hz, 1H), 2.65 (s, 3H),
1.82 (m, 2H), 1.70 (m, 2H). 13C NMR: 202.3, 167.4, 161.6,
146.3, 138.5, 133.4, 129.5, 128.6, 127.9, 80.5, 77.7, 66.2,
53.7, 51.8, 36.7, 33.0, 26.8. Anal. Calcd for
C17H21N3O3ÆHCl: C, 58.03; H, 6.30; N, 11.94; Cl, 10.08.
Found: C, 58.13; H, 6.28; N, 11.85; Cl, 10.15. Compound
25
294 ꢁC.½aꢀD +12.4 (c 0.51, EtOH). 1H NMR: 8.24 (d,
J = 7.2 Hz, 1H), 8.18 (s, 1H), 7.75 (d, J = 7.2 Hz, 1H), 7.64
(t, J = 7.2 Hz, 1H), 5.05 (d, J = 16.8 Hz, 1H), 4.85 (d,
J = 16.8 Hz, 1H), 3.44 (m, 1H), 3.31 (m, 1H), 3.29 (dd,
J = 17.2 and 5.5 Hz, 1H), 2.93 (m, 2H), 2.85 (dd, J = 17.2
and 4.7 Hz, 1H), 1.82 (m, 2H), 1.71 (m, 2H), 1.31 (s, 9H).
13C NMR: 202.3, 169.5, 165.1, 152.9, 147.2, 143.1, 133.9,
130.1, 129.9, 81.0, 72.1, 63.5, 56.8, 51.5, 37.3, 35.6, 31.8,
30.5. Anal. Calcd for C20H27N3O3ÆHCl: C, 60.98; H, 7.16;
N, 10.67; Cl, 9.00. Found: C, 60.91; H, 7.19; N, 10.56; Cl,
9.09. Compound 13 (hydrochloride salt): mp: 290–291 ꢁC.
25
18 (hydrochloride salt): mp: 272–273 ꢁC. ½aꢀD ꢁ11.6 (c
1
0.45, EtOH). H NMR: 8.18 (s, 1H), 7.85 (d, J = 7.2 Hz,
1H), 7.64 (t, J = 7.2 Hz, 1H), 7.45 (d, J = 7.2 Hz, 1H), 5.04
(d, J = 16.7 Hz, 1H), 4.89 (d, J = 16.7 Hz, 1H), 3.40 (m,
1H), 3.39 (m, 1H), 3.25 (dd, J = 17.1 and 5.7 Hz, 1H), 2.92
(m, 2H), 2.81 (dd, J = 17.1 and 4.9 Hz, 1H), 2.61 (s, 3H),
1.80 (m, 2H), 1.71 (m, 2H). 13C NMR: 202.4, 167.2, 161.3,
147.3, 137.4, 134.4, 129.9, 129.0, 128.3, 80.2, 77.1, 66.0,
53.4, 51.5, 36.3, 33.2, 26.9. Anal. Calcd for
C17H21N3O3ÆHCl: C, 58.03; H, 6.30; N, 11.94; Cl, 10.08.
Found: C, 58.09; H, 6.35; N, 11.80; Cl, 10.25. Compound
25
½aꢀD ꢁ10.3 (c 0.45, EtOH). 1H NMR: 8.21 (s, 1H), 7.96 (d,
J = 7.1 Hz, 1H), 7.68 (d, J = 7.1 Hz, 1H), 7.55 (s, 1H), 5.06
(d, J = 16.8 Hz, 1H), 4.90 (d, J = 16.8 Hz, 1H), 3.44 (m,
1H), 3.29 (m, 1H), 3.25 (dd, J = 17.2 and 5.7 Hz, 1H), 2.89
(m, 2H), 2.77 (dd, J = 17.2 and 4.8 Hz, 1H), 1.80 (m, 2H),
1.71 (m, 2H), 1.34 (s, 9H). 13C NMR: 202.9, 167.9, 164.6,
154.1, 143.2, 134.7, 129.9, 128.8, 128.4, 81.1, 71.2, 65.5,
55.7, 52.3, 37.4, 35.5, 32.7, 30.2. Anal. Calcd for
C20H27N3O3ÆHCl: C, 60.98; H, 7.16; N, 10.67; Cl, 9.00.
Found: C, 60.89; H, 7.13; N, 10.60; Cl, 9.12. Compound
25
19 (hydrochloride salt): mp: 281–282 ꢁC.½aꢀD +18.3 (c 0.5,
EtOH). 1H NMR: 8.11 (s, 1H), 7.71 (s, 1H), 7.22 (d,
J = 7.2 Hz, 1H), 7.42 (d, J = 7.2 Hz, 1H), 5.05 (d,
J = 16.7 Hz, 1H), 4.90 (d, J = 16.7 Hz, 1H), 3.81 (s, 3H),
3.49 (m, 1H), 3.28 (m, 1H), 3.20 (dd, J = 17.1 and 5.8 Hz,
1H), 2.80 (m, 2H), 2.74 (dd, J = 17.1 and 4.9 Hz, 1H), 1.82
(m, 2H), 1.72 (m, 2H). 13C NMR: 202.5, 168.3, 165.5,
161.3, 188.5, 138.4, 134.5, 130.6, 128.9, 81.5, 77.5, 66.0,
58.7, 53.5, 52.8, 37.1, 32.2. Anal. Calcd for
C17H21N3O4ÆHCl: C, 55.51; H, 6.03; N, 11.42; Cl, 9.64.
Found: C, 55.63; H, 6.08; N, 11.55; Cl, 9.75. Compound
25
14 (dihydrochloride salt): mp: 341–342 ꢁC (dec). ½aꢀD
+27.4 (c 0.43, EtOH). 1H NMR: 9.25 (s, 1H), 8.76 (d,
J = 7.3 Hz, 1H), 8.48 (d, J = 7.3 Hz, 1H), 8.26 (s, 1H), 5.07
(d, J = 16.7 Hz, 1H), 4.93 (d, J = 16.7 Hz, 1H), 3.42 (m,
1H), 3.27 (m, 1H), 3.28 (dd, J = 17.3 and 5.8 Hz, 1H), 2.92
(m, 2H), 2.78 (dd, J = 17.3 and 4.7 Hz, 1H), 1.81 (m, 2H),
1.70 (m, 2H). 13C NMR: 202.6, 167.9, 164.6, 159.1, 155.2,
154.7, 139.9, 134.8, 81.0, 71.9, 66.5, 55.6, 52.1, 37.6, 32.5.
Anal. Calcd for C15H18N4O3Æ2HCl: C, 48.01; H, 5.37; N,
14.93. Found: C, 48.12; H, 5.33; N, 14.84. Compound 15
25
20 (hydrochloride salt): mp: 282–283 ꢁC. ½aꢀD ꢁ15.6 (c 0.5,
1
EtOH). H NMR: 8.13 (s, 1H), 7.54 (t, J = 7.3 Hz, 1H),
7.35 (d, J = 7.3 Hz, 1H), 7.15 (d, J = 7.3 Hz, 1H), 5.02 (d,
J = 16.9 Hz, 1H), 4.89 (d, J = 16.9 Hz, 1H), 3.77 (s, 3H),
3.41 (m, 1H), 3.36 (m, 1H), 3.27 (dd, J = 17.4 and 5.7 Hz,
1H), 2.92 (m, 2H), 2.81 (dd, J = 17.4 and 4.9 Hz, 1H), 2.64
(s, 3H), 1.79 (m, 2H), 1.68 (m, 2H). 13C NMR: 203.1,
166.2, 162.3, 160.5, 147.3, 137.4, 132.9, 129.9, 128.7, 80.1,
76.1, 66.5, 58.9, 53.1, 51.3, 36.7, 33.0. Anal. Calcd for
C17H21N3O4ÆHCl: C, 55.51; H, 6.03; N, 11.42; Cl, 9.64.
Found: C, 55.44; H, 6.05; N, 11.52; Cl, 9.55.
25
(dihydrochloride salt): mp: 341–342 ꢁC (dec). ½aꢀD ꢁ19.6
1
(c 0.42, EtOH). H NMR: 8.93 (d, J = 6.8 Hz, 1H), 8.78
(d, J = 6.8 Hz, 1H), 8.31 (s, 1H), 8.25 (t, J = 6.8 Hz, 1H),
4.92 (d, J = 17.2 Hz, 1H), 4.81 (d, J = 17.2 Hz, 1H), 3.51
(m, 1H), 3.33 (m, 1H), 3.21 (dd, J = 17.2 and 5.6 Hz, 1H),
2.81 (m, 2H), 2.78 (dd,J = 17.2 and 4.5 Hz, 1H), 1.89 (m,
2H), 1.67 (m, 2H). 13C NMR: 204.1, 171.8, 167.3, 162.8,
152.1, 142.6, 133.1, 130.9, 81.4, 70.8, 65.8, 52.7, 50.9, 37.6,
31.8. Anal. Calcd for C15H18N4O3Æ2HCl: C, 48.01; H,
5.37; N, 14.93. Found: C, 47.90; H, 5.45; N, 14.81.
19. Williams, E. J.; Kenny, P. W.; Kettle, J. G.; Mwashimba,
P. G. Tetrahedron Lett. 2004, 45, 3737.
20. Alexandre, F. R.; Berecibar, A.; Besson, T. Tetrahedron
Lett. 2002, 43, 3911.
21. Armarego, W. L. F.; Smith, J. I. C. J. Chem. Soc. B 1967,
449.
22. Desjardins, R. E.; Canfield, C. J.; Haynes, D. E.; Chulay,
J. D. Antimicrob. Agents Chemother. 1979, 16, 710.
23. Chulay, J. D.; Haynes, J. D.; Diggs, C. L. Exp. Parasitol.
1983, 55, 138.
25
Compound 16 (hydrochloride salt): mp: 298–299 ꢁC. ½aꢀD
+14.6 (c 0.5, EtOH). 1H NMR: 8.21 (s, 1H), 7.85 (d,
J = 7.2 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.55 (d,
J = 7.2 Hz, 1H), 5.03 (d, J = 16.8 Hz, 1H), 4.87 (d,
J = 16.8 Hz, 1H), 3.41 (m, 1H), 3.34 (m, 1H), 3.26 (dd,
J = 17.1 and 5.5 Hz, 1H), 2.90 (m, 2H), 2.84 (dd, J = 17.1
and 4.7 Hz, 1H), 1.83 (m, 2H), 1.70 (m, 2H). 13C NMR:
204.4, 167.8, 164.8, 149.9, 142.2, 134.3, 130.9, 129.1, 127.6,
81.1, 72.4, 64.5, 54.8, 51.8, 37.2, 31.6. Anal. Calcd for
24. Fontaine, F.; de Sousa, G.; Duchene, P.; Rahmani, R.
Toxicology In Vitro 1998, 12, 545.