U. Kucklaender et al. / Bioorg. Med. Chem. 19 (2011) 2666–2674
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CH3), 1.15 (t, J = 7.0 Hz, 3H, COOCH2CH3), MS 465 (40, M+), 436
(47), 419 (61), 395 (53), 329 (42), 313 (26), 267 (100), Anal. Calcd
for C20H14Cl3N3O4 (466.71): C, 51.47; H, 3.02; N, 9.00. Found: C,
51.00; H, 2.94; N, 8.85.
0.81 (t, J = 7.0 Hz, 3H, COOCH2CH3). MS (FAB + NBA) 508 (M++1).
26H19Cl2N3O4 (508.36).
C
5.2.9. Ethyl-8,9-dichlor-6-cyano-7-hydroxy-1-imino-2-(4-
fluorbenzyl)-10-oxo-3-phenyl-2-aza-spiro[4.5]deca-3,6,8-trien-
4-carboxylate 7i
5.2.4. Ethyl-8,9-dichloro-6-cyano-7-hydroxy-1-imino-2-(4-
bromophenyl)-3-methyl-10-oxo-2-aza-spiro[4.5]deca-3,6,8-
triene-4-carboxylate 7d
1.36 g (6.01 mmol) DDQ 5a, 1,5 g (5,01 mmol) 2i, 6 ml glacial
acetic acid, 1,13 g (43%), mp168 °C (orange powder). IR 2184,
1684. 1H NMR (DMSO-d6) d 11.26 (br s, 1H, @NH), 10.91 (br s,
1H, OH), 7.68–6.94 (m, 9H, arom. H), 4.87 (s, 2H, CH2), 3.86 (q,
J = 7.0 Hz, 2H, COOCH2), 0.82 (t, J = 7.0 Hz, 3H, COOCH2CH3). MS
525 (2; M+), 331 (8), 375 (5), 347 (4), 330 (6), 329 (7), 109 (100).
Anal. Calcd for C26H18Cl2FN3O4 (526.35): C, 59.37; H, 3.45; N,
7.98. Found.: C, 59.41; H, 3,22; N, 7,66.
1.1 g DDQ 5a (4.84 mmol), 1.1 g (4.04 mmol) 2d, 5 ml glacial
acetic acid, 1.5 g (71%), mp 230 °C (yellow-orange powder from
glacial acetic acid). IR 2181, 1697, 1673. 1H NMR (DMSO-d6) d
11.33 (br s, 1H, @NH), 10.39 (br s, 1H, OH), 8.05–7.06 (m, 4H, arom.
H), 4.08 (q, J = 7.0 Hz, 2H, COOCH2CH3), 2.27 (s, 3H, CH3), 1.10 (t,
J = 7.0 Hz, 3H, COOCH2CH3). MS 511 (45, M+), 482 (10), 430 (7),
314 (24), 267 (32), 228 (68), 198 (35), 87 (16), 40 (22), 35 (100).
Anal. Calcd for C20H14BrCl2N3O4 (511.16): C, 47.00; H, 2.76; N,
8.22. Found: C, 46.86; H, 2.41; N, 8.07.
5.2.10. Ethyl-8,9-dichloro-6-cyano-7-hydroxy-1-imino-2-(4-
methoxyphenyl)-10-oxo-3-phenyl-2-aza-spiro[4.5]deca-3,6,8-
triene-4-carboxylate 7j
5.2.5. Ethyl-8,9-dichloro-6-cyano-7-hydroxy-1-imino-2-
isobutyl-3-methyl-10-oxo-2-aza-spiro[4.5]deca-3,6,8-triene-4-
carboxylate 7e
274 mg DDQ 5a (1.21 mmol), 300 mg (1.00 mmol) 2j, 3 ml
glacial acetic acid, 266 mg (51%), mp 220 °C (orange-red powder
from glacial acetic acid). IR 2185, 1704, 1670. 1H NMR (DMSO-
d6) d 11.38 (br s, 1H, @NH), 10.23 (br s,1H, OH), 7.53–6.78 (m,
9H, arom H), 4.89 (s, 3H, OCH3), 3.89 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 0.85 (t, J = 7.0 Hz, 3H, COOCH2CH3). MS 523 (49,
M+), 495 (87), 374 (92), 329 (100). Anal. Calcd for C26H19Cl2N3O5
(524.36): C,59.56; H, 3.56; N, 8.01. Found: C, 59.33; H, 3.44; N,
7.90.
1.9 g DDQ 5a (8.37 mmol), 1.3 g (7.01 mmol) 2e, 8.5 ml glacial
acetic acid, 2.65 g (92%), mp 174 °C (orange powder from glacial
acetic acid). IR 2190, 1698, 1682. 1H NMR (DMSO-d6) d 10.93 (br
s, 1H, @NH), 10.54 (br s, 1H, OH), 4.03 (q, J = 7.0 Hz, 2H,
COOCH2CH3), 3.67 (d, J = 7.5 Hz, CH2), 2.53 (s, 3H, CH3), 2.02 (m,
1H, CH), 1.07 (t, J = 7.0 Hz, 3H, COOCH2CH3), 0.94 (m, 6H,
2 ꢁ CH3–isobutyl), MS 411 (26, M+), 327 (41), 282 (39), 267
(100). Anal. Calcd for C18H19Cl2N3O4 (412.28): C, 52.44; H, 4.65;
N, 10.19 Found: C, 52.34; H, 4.86; N, 9.80.
5.2.11. 4-Benzoyl-8,9-dichlor-6-cyano-7-hydroxy-1-imino-2-
phenyl-10-oxo-3-phenyl-2-aza-spiro[4.5]deca-3,6,8-trien 7k
575 mg (2,53 mmol) DDQ 5a, 500 mg (2,1 mmol) 2k, 2 ml
glacial acetic acid, 185 mg (19%), mp 130 °C, orange powder.
IR 2179, 1682. 1H NMR (DMSO-d6) d 11.23 (br s, 1H, NH),
10.22 (s, 1H, OH), 7.84–7.33 (m, 10H, arom. H), 1.65 (s, 3H,
CH3). MS 464 (6; M+), 393 (87), 345 (38), 268 (13), 183 (9),
5.2.6. Ethyl-8,9-dichloro-6-cyano-7-hydroxy-1-imino-2-(2,4-
difluorophenyl)-3-methyl-10-oxo-2-aza-spiro[4.5]deca-3,6,8-
triene-4-carboxylate 7f
1.921 g DDQ 5a (8.46 mmol), 1.7 g (7.05 mmol) 2f, 5 ml glacial
acetic acid, 2.43 g (74%), mp 212 °C (yellow-orange powder from
glacial acetic acid). IR 2186, 1702, 1672. 1H NMR (DMSO-d6) d
11.54–8.32 (br s, 2H, @NH, –OH), 7.87–7.22 (m, 3H, arom H),
4.08 (q, J = 7.0 Hz, 2H, COOCH2CH3), 2.20 (s, 3H, CH3), 1.10 (t,
J = 7.0 Hz, 3H, COOCH2CH3). MS 467 (32, M+), 440 (24), 386 (12),
317 (5), 228 (65), 154 (100), Anal. Calcd for C20H13Cl2F2N3O4
(468.25): C, 51.30; H, 2.80; N, 8.97. Found: C, 51.12; H, 2.62; N,
9.17.
118 (60), 77 (100), 51 (58). Anal. Calcd for
C24H15Cl2N3O3
(464,30): C: 62,08; H: 3,26; N: 9,05. found: C, 61.83; H, 3.28;
N, 8,65.
5.2.12. Ethyl-6-cyano-7-hydroxy-1-imino-2-(4-tolyl)-3-methyl-
10-oxo-2-aza-spiro[4.5]deca-3,6,8-triene-4-carboxylate 7l
300 mg 2,3-dicyan-p-benzoquinone 5b (1.89 mmol), 202 mg
(1.89 mmol) 2l, 3 ml nitromethan, 434 mg (61%), mp 197 °C (yel-
low powder from nitromethan). IR 2185, 1704, 1670. 1H NMR
(DMSO-d6) d 11.65 (s, br s, 1H, @NH), 8.56 (s, br, 1H, OH), 7.44–
6.98 (m, 4H, arom H’s), 7.23 (d, J = 10.1 Hz, 1H, H-8), 6.41 (d,
J = 10.1 Hz, 1H, H-7), 4.1 (mc, 2H, COOCH2CH3), 2.37 (s, 3H, CH3),
2.18 (s, 3H, CH3), 1.09 (t, J = 7.0 Hz, 3H, COOCH2CH3). MS 377
(100, M+), 349 (21), 331 (40), 320 (15), 276 (40), 223 (32), 132
(67). Anal. Calcd for C21H19N3O4 (377.40): C, 66.83; H, 5.07;
N,11.13. Found: C, 66.63; H, 4.80; N, 10.86.
5.2.7. Ethyl-8,9-dichloro-6-cyano-7-hydroxy-1-imino-2-(4-
methoxyphenyl)-3-methyl-10-oxo-2-aza-spiro[4.5]deca-3,6,8-
triene-4-carboxylate 7g
930 mg DDQ 5a (3.93 mmol), 770 mg (3.27 mmol) 2g, 5 ml gla-
cial acetic acid, 1.13 g (75%), mp 238 °C, (orange powder from gla-
cial acetic acid). IR 2179, 1703, 1673. 1H NMR (DMSO-d6) d 11.42
(s, br s, 1H, @NH),10.19 (s, br s, 1H, OH), 7.57–7.05 (m, 4H, arom.
H), 4.07 (q, J = 7.0 Hz, 2H, COOCH2CH3), 3.68 (s, 3H, OCH3), 2.18
(s, 3H, CH3), 1.09 (t, J = 7.0 Hz, 3H, CH3). MS 461 (15, M+), 416
(25), 398 (10), 388 (20), 335 (34), 317 (13), 267 (46), 148 (100).
Anal. Calcd for C21H17Cl2N3O5 (462.29): C, 54.56; H, 3.71; N, 9.09.
Found: C, 54.36; H, 3.58; N, 9.00
5.2.13. Ethyl-6-cyano-7-hydroxy-1-imino-2-(4-bromophenyl)-
3-methyl-10-oxo-2-aza-spiro[4.5]deca-3,6,8-triene-4-
carboxylate 7m
300 mg 2,3-dicyan-p-benzoquinone 5b (1.89 mmol), 325 mg
(1.89 mmol) 2m, 1.5 ml nitromethan and 0.75 ml glacial acetic
acid, 343 mg (42%), mp180 °C (yellow powder from nitromethan).
IR 2193, 1693, 1666. 1H NMR (DMSO-d6) d 11.74 (s, br s, 1H, @NH),
8.74 (s, br, 1H, OH), 7.84–7.09 (m, 4H, arom H), 7.24 (d, 2J = 10.2 Hz,
1H, H-8), 6.41 (d, 2J = 10.2 Hz, 1H, H-7), 4.1 (mc, 2H, COOCH2CH3),
2.21 (s, 3H, CH3), 1.09 (t, J = 7.0 Hz, 3H, COOCH2CH3). MS 443 (35,
M+), 397 (85), 355 (46), 300 (36), 245 (33), 199 (100), Anal. Calcd
for C20H16BrN3O4 (442.27): C, 54.32; H, 3.65; N, 9.50. Found: C,
53.90; H, 3.36; N, 9.26.
5.2.8. Ethyl-8,9-dichloro-6-cyano-7-hydroxy-1-imino-2-benzyl-
10-oxo-3-phenyl-2-aza-spiro[4.5]deca-3,6,8-triene-4-
carboxylate 7h
234 mg DDQ 5a (1.03 mmol), 300 mg (0.86 mmol) 2h, 3 ml gla-
cial acetic acid, 310 mg (71%), mp 173 °C (orange powder from gla-
cial acetic acid). IR 2190, 1706, 1686. 1H NMR (DMSO-d6) d 11.24 (s,
br s, 1H, @NH), 10.85 (s, br s,1H, OH), 7.58–6.97 (m, 10H, arom H),
4.89 (q, 2H, CH2–benzyl), 4.01–3.72 (q, J = 7.0 Hz, 2H, COOCH2CH3),