3146 J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 19
4-Hyd r oxy-3-m eth oxy-N′-[(E)-1-n a p h th ylm eth ylid en e]-
Ling et al.
N′-[(E)-(1,1′-Bip h en yl]-4-ylm eth ylid en e]-4-h yd r oxy-3-
m eth oxyben zoh yd r a zid e (14). Yield 23%; mp 205-206 °C;
1H NMR (DMSO-d6) δ 4.02 (s, 3H), 7.04 (d, J ) 8.2 Hz, 1H),
7.63-7.68 (m, 5H), 7.88-7.96 (m, 6H), 8.65 (s, 1H), 9.90 (br s,
1H), 11.83 (s, 1H); MS (APCI) m/z 347.09 (M+H+). Anal.
(C21H18N2O3) C, H, N.
1
ben zoh yd r a zid e (3). Yield 64%; mp 165-167 °C; H NMR
(DMSO-d6) δ 3.94 (s, 3H), 6.74 (d, J ) 8.2 Hz, 1H), 7.37-7.52
(m, 6H), 7.77 (d, J ) 7.1 Hz, 1H), 7.85 (m, 2H), 8.67 (d, J )
8.1 Hz, 1H), 9.13 (s, 1H), 10.90 (br s, 1H); MS (APCI) m/z
321.07 (M+H+). Anal. (C19H16N2O3‚0.5H2O) C, H, N.
N ′-{(E )-[5-(3-Ch lor o-4-m e t h ylp h e n yl)-2-fu r yl]m e t h -
ylid en e}-4-h yd r oxy-3-m eth oxyben zoh yd r a zid e (15). Yield
76.7%; mp 210-212 °C; 1H NMR (DMSO-d6) δ 3.85 (s, 3H),
6.89 (d, J ) 9.0 Hz, 1H), 7.05 (d, J ) 3.0 Hz, 1H), 7.28 (s, 1H),
7.48 (m, 4H), 7.74 (d, J ) 3.0 Hz, 1H), 7.84 (s, 1H), 8.39 (s,
1H), 9.77 (s, 1H), 11.67 (s, 1H). Anal. (C19H15ClN2O4‚0.4H2O)
C, H, N.
4-Hyd r oxy-3-m eth oxy-N′-[(E)-(4-m eth oxy-1-n a p h th yl)-
m eth ylid en e]ben zoh yd r a zid e (4). mp 184.5-186 °C; 1H
NMR (CDCl3) δ 3.86 (s, 3H), 4.80 (s, 3H), 6.00 (s, 1H), 6.59 (d,
1H), 6.83 (d, 1H), 7.39 (m, 3H), 7.52 (s, 1H), 7.73 (s, 1H), 8.18
(d, 1H), 8.58 (d, 1H), 8.88 (s, 1H), 9.95 (s, 1H); MS (APCI) m/z
351 (M+H+). Anal. (C20H18N2O4) C, H, N.
N′-[(E)-(2,4-Dioxo-1,2,3,4-tetr a h yd r o-5-p yr id in yl)m eth -
ylid en e]-4-h yd r oxy-3-m eth oxyben zoh yd r a zid e (5). Yield
66%; mp 259-261 °C; 1H NMR (DMSO-d6) δ 3.77 (s, 3H), 6.78
(d, J ) 8.2 Hz, 1H), 7.36 (d, J ) 8.3 Hz, 1H), 7.40 (s, 1H), 7.82
(s, 1H), 8.27 (s, 1H), 9.66 (br s, 1H), 11.20 (br s, 1H), 11.37 (s,
1H), 11.45 (s, 1H); MS (APCI) m/z 304.97 (M+H+). Anal.
(C13H12N4O5‚0.9H2O) C, H, N.
4-Hyd r oxy-N′-[(E)-1H-in d ol-3-ylm eth ylid en e]-3-m eth -
oxyben zoh yd r a zid e (16). Yield 45%; mp 224-226 °C; 1H
NMR (DMSO-d6) δ 3.79 (s, 3H), 6.80 (d, J ) 8.2 Hz, 1H), 7.11
(m, 2H), 7.39 (m, 3H), 7.74 (s, 1H), 8.23 (d, J ) 7.5 Hz, 1H),
8.54 (s, 1H), 9.58 (s, 1H), 11.23 (s, 1H), 11.50 (s, 1H); MS
(APCI) m/z 310.06 (M+H+). Anal. (C17H15N3O3) C, H, N.
N′-[(E)-(9-E t h yl-9H -ca r b a zol-3-yl)m et h ylid en e]-4-h y-
d r oxy-3-m eth oxyben zoh yd r a zid e (17). This was recrystal-
lized from ethanol in 26% yield; mp 126-128 °C dec; 1H NMR
(DMSO-d6) δ 1.33 (t, J ) 6.80 Hz, 3H), 3.86 (s, 3H), 4.49 (q, J
) 7.18 Hz, 2H), 6.89 (d, J ) 7.93 Hz, 1H), 7.25 (t, J ) 7.37,
1H), 7.49 (m, 3H), 7.68 (m, 2H), 7.89 (d, J ) 8.31 Hz, 1H),
8.24 (d, J ) 7.55 Hz, 1H), 8.46 (s, 1H), 8.61 (s, 1H), 9.71 (s,
1H), 11.56 (s, 1H). Anal. (C23H21N3O3‚1EtOH) C, H, N.
4-Hydr oxy-3-m eth oxy-N′-[(E)-4-qu in olin ylm eth yliden e]-
ben zoh yd r a zid e (18). Yield 76%; 1H NMR (DMSO-d6) δ 3.58
(s, 3H), 6.52 (d, J ) 8.1 Hz, 1H), 7.28 (m, 2H), 7.48 (t, J ) 7.1
Hz, 1H), 7.61 (m, 2H), 7.86 (d, J ) 8.4 Hz, 1H), 8.49 (d, J )
8.4 Hz, 1H), 8.73 (d, J ) 4.5 Hz, 1H), 8.94 (s, 1H); MS (APCI)
m/z 322.08 (M+H+). Anal. (C18H15N3O3‚0.25H2O) C, H, N.
N′-{(E)-[4-(Dim eth yla m in o)-1-n a p h th yl]m eth ylid en e}-
4-h yd r oxy-3-m eth oxyben zoh yd r a zid e (19). Yield 39%; mp
4-Hyd r oxy-3-m eth oxy-N′-[(E)-(5-m eth yl-1H-im id a zol-4-
yl)m eth ylid en e]ben zoh yd r a zid e (6). Yield 99%; mp 264 °C,
1
dec; H NMR (DMSO-d6) δ 2.60 (s, 3H), 3.99 (s, 3H), 8.72 (s,
1H), 14.52 (br s, 1H); MS (APCI) m/z 274.99 (M+H+). Anal.
(C13H14N4O3‚0.75H2O) C, H, N.
4-Hyd r oxy-3-m eth oxy-N′-[(E)-(4-m eth oxyp h en yl)m eth -
ylid en e]ben zoh yd r a zid e (7). Yield 73%; mp 202-203 °C; 1H
NMR (DMSO-d6) δ 3.80 (s, 3H), 3.84 (s, 3H), 6.86 (d, J ) 8.29
Hz, 1H), 7.01 (d, J ) 8.67 Hz, 2H), 7.43 (d, J ) 9.42 Hz, 1H),
7.47 (s, 1H), 7.64 (d, J ) 8.67 Hz, 2H), 8.38 (s, 1H), 9.61 (s,
1H), 11.34 (s, 1H); MS (APCI) m/z 301.05 (M+H+). Anal.
(C16H16N2O7 ) C, H, N.
4-Hyd r oxy-N′-[(E)-(4-h yd r oxyp h en yl)m eth ylid en e]-3-
m eth oxyben zoh yd r a zid e (8). Yield 48%; mp 250-252 °C;
1H NMR (DMSO-d6) δ 3.84 (s, 3H), 6.84 (m, 3H), 7.42 (dd, J )
8.29 Hz, 1.88 Hz, 1H), 7.47 (d, J ) 1.88 Hz, 1H), 7.53 (d, J )
8.29 Hz, 2H), 8.32 (s, 1H), 9.59 (s, 1H), 9.82 (s, 1H), 11.35 (s,
1H); MS (APCI) m/z 287.05 (M+H+). Anal. (C15H14N2O7 ) C,
H, N.
1
221-222 °C; H NMR (DMSO-d6) δ 3.05 (s, 6H), 3.97 (s, 3H),
7.06 (d, J ) 8.2 Hz, 1H), 7.33 (d, J ) 8.0 Hz, 1H), 7.66 (m,
2H), 7.77 (m, 2H), 7.97 (d, J ) 7.9 Hz, 1H), 8.38 (d, J ) 7.9
Hz, 1H), 9.10 (d, J ) 8.2 Hz, 1H), 9.14 (s, 1H), 9.90 (s, 1H),
11.74 (s, 1H);MS (APCI)m/z364.08 (M+H+). Anal. (C21H21N3O3‚
0.5H2O) C, H, N.
4-Hyd r oxy-N′-[(E)-(3-h yd r oxy-4-m eth oxyp h en yl)m eth -
ylid en e]-3-m eth oxyben zoh yd r a zid e (9). Yield 22%; mp
1
188-189 °C; H NMR (DMSO-d6) δ 3.79 (s, 3H), 3.84 (s, 3H),
4-Hydr oxy-N′-[(E)-(4-h ydr oxy-1-n aph th yl)m eth yliden e]-
3-m eth oxyben zoh yd r a zid e (20). Yield 75%; mp 230.5-
231.5; 1H NMR (DMSO-d6) δ 3.86 (s, 3H), 6.89 (d, J ) 7.9 Hz,
1H), 6.96 (d, J ) 7.9 Hz, 1H), 7.48 (m, 3H), 7.63 (dd, J ) 7.9,
7.2 Hz, 1H), 7.72 (d, J ) 7.9 Hz, 1H), 8.23 (d, J ) 8.7 Hz, 1H),
8.92 (m, 2H), 9.62 (br s, 1H), 10.69 (s, 1H), 11.44 (s, 1H); MS
(APCI) m/z 337 (M+H+). Anal. (C19H16N2O4‚1.45H2O) C, H, N.
4-Hydr oxy-N′-[(E)-(4-m eth oxy-1-n aph th yl)m eth yliden e]-
ben zoh yd r a zid e (21). Yield 68.1%; mp 230.5-233 °C; 1H
NMR (DMSO-d6) δ 3.95 (s, 3H), 6.81 (d, J ) 8.58 Hz, 2H), 7.03
(d, J ) 8.2 Hz, 1H), 7.53 (t, J ) 7.7 Hz, 1H), 7.62 (t, J ) 6.8
Hz, 1H), 7.77 (m, 3H), 8.19 (d, J ) 8.2 Hz, 1H), 8.89 (m, 2H),
10.07 (s, 1H);MS (APCI)m/z321.06 (M+H+). Anal. (C19H16N2O3‚
0.6H2O) C, H, N.
3-Meth oxy-N′-[(E)-(4-m eth oxy-1-n aph th yl)m eth yliden e]-
ben zoh yd r a zid e (22). Yield 39%; 1H NMR (DMSO-d6) δ 3.91
(s, 3H), 4.10 (s, 3H), 7.50-6.61 (m, 3H), 7.65 (t, J ) 9 Hz, 1H),
7.76 (t, J ) 9 Hz, 1H), 7.92 (d, J ) 9 Hz, 1H), 8.32 (d, J ) 9
Hz, 1H), 9.03 (s, 1H), 9.06 (s, 1H), 11.79 (s, 1H); MS (APCI)
m/z 335.09 (M+H+). Anal. (C20H18N2O3) C, H, N.
6.85 (d, J ) 8.29 Hz, 1H), 6.92 (d, J ) 8.29, 1H), 7.02 (d, J )
8.29 Hz, 1H), 7.25 (s, 1H), 7.42 (dd, J ) 8.29, 1.88 Hz, 1H),
7.47 (d, J ) 1.51 Hz, 1H), 8.26 (s, 1H), 9.21 (s, 1H), 9.60 (s,
1H), 11.37 (s, 1H); MS (APCI) m/z 317.07 (M+H+). Anal.
(C16H16N2O5‚0.1H2O) C, H, N.
4-H yd r oxy-3-m et h oxy-N′-{(E)-[4-(t r iflu or om et h oxy)-
p h en yl]m eth ylid en e}ben zoh yd r a zid e (10). Yield 53%; mp
1
202-203 °C; H NMR (DMSO-d6) δ 4.01 (s, 3H), 7.06 (d, J )
8.11 Hz, 1H), 7.64 (m, 4H), 8.03 (d, J ) 8.81 Hz, 2H), 8.64 (s,
1H), 9.93 (s, 1H), 11.89 (s, 1H); MS (APCI) m/z 355.00 (M+H+).
Anal. (C16H13F3N2O4) C, H, N.
4-Hyd r oxy-3-m eth oxy-N′-(E)-{4-[(E)-2-p h en yleth en yl]-
p h en yl}m eth ylid en e]ben zoh yd r a zid e (11). Yield 75%; mp
1
238-239 °C; H NMR (DMSO-d6) δ 3.82 (s, 3H), 6.84 (d, 1H,
J ) 7.91 Hz), 7.27 (dd, J ) 7.54, 6.78 Hz, 1H), 7.33 (d, J )
4.52 Hz, 2H), 7.38 (t, J ) 7.54 Hz, 2H), 7.44 (dd, J ) 8.29,
1.88 Hz, 1H), 7.47 (s, 2H), 7.62 (d, J ) 7.54 Hz, 2H), 7.70 (m,
4H), 8.42 (s, 1H), 11.64 (s, 1H); MS (APCI) m/z 373.07 (M+H+).
Anal. (C23H20N2O3‚2H2O) C, H, N.
4-Hyd r oxy-N′-[(E)-(4-isop r op ylp h en yl)m eth ylid en e]-3-
m eth oxyben zoh yd r a zid e (12). Yield 45%; mp 192-193.5 °C;
1H NMR (CDCl3) δ 1.23 (d, J ) 7.2 Hz, 6H), 2.91 (septet, 1H),
3.93 (s, 3H), 6.00 (br s, 1H), 6.95 (d, J ) 7.9 Hz, 1H), 7.22 (m,
3H), 7.52 (m, 1H), 7.63 (m, 2H), 8.24 (br s, 1H), 9.37 (br s,
1H); MS (APCI) m/z 313.07 (M+H+). Anal. (C18H20N2O3‚
0.33H2O) C, H, N.
4-Hyd r oxy-N′-[(E)-(4-ter t-bu tylp h en yl)m eth ylid en e]-3-
m eth oxyben zoh yd r a zid e (13). Yield 49%; mp 135-139 °C;
1H NMR (CDCl3) δ 1.31 (s, 9H), 3.92 (s, 3H), 6.06 (br s, 1H),
6.92 (d, J ) 7.54, 1H), 7.38 (m, 3H), 7.54 (m, 1H), 7.63 (m,
2H), 8.28 (br s, 1H), 9.59 (br s, 1H); MS (APCI) m/z 327.08
(M+H+). Anal. (C19H22N2O3‚0.7H2O) C, H, N.
4-Hydr oxy-N′-[(E)-(4-h ydr oxy-1-n aph th yl)m eth yliden e]-
ben zoh yd r a zid e (23). Yield 40%; mp 258-260 °C; H NMR
1
(DMSO-d6) δ 6.85 (d, 2H, J ) 8.7 Hz), 6.95 (d, J ) 7.9 Hz,
1H), 7.52 (t, J ) 7.5 Hz, 1H), 7.63 (t, J ) 7.5 Hz, 1H), 7.71 (d,
J ) 7.9 Hz, 1H), 7.83 (d, J ) 8.7 Hz, 2H), 8.23 (d, J ) 7.9 Hz,
1H),8.94 (m, 2H), 10.11 (s, 1H), 10.76 (s, 1H), 11.50 (s, 1H);
MS (APCI) m/z 307.06 (M+H+). Anal. (C18H14N2O3‚0.25H2O)
C, H, N.
3-Am in o-4-h yd r oxy-N′-[(E)-(4-h yd r oxy-1-n a p h th yl)m -
eth ylid en e]ben zoh yd r a zid e (24). Yield 92%; mp 254-260
1
°C dec; H NMR (DMSO-d6) δ 6.66 (dd, J ) 8.2, 1.2 Hz, 1H),
6.90 (d, J ) 7.3 Hz, 1H), 7.02 (d, J ) 8.2 Hz, 1H), 7.15 (s, 1H),
7.46 (t, J ) 7.1 Hz, 1H), 7.56 (t, J ) 7.9 Hz, 1H), 7.63 (d, J )