May 2011
Pyrazoles and Pyrazolo[4,3-e]pyrrolo[1,2-a]pyrazines II
683
(40), 355 (Mþ) (100), 354 (M ꢁ 1) (15), 327 (7), 311 (14), 310
(43), 208 (9), 179 (10), 177 (14), 169 (38), 159 (15), 155 (5),
77 (35). Anal. Calcd. for C22H21N5 (355.44): C, 74.34; H, 5.96;
N, 19.70. Found: C, 74.45; H, 5.99; N, 19.64.
under reflux for 8 h. The solvent was removed under reduced
pressure, and the residue formed was diluted with water. The
solid product obtained was filtered off, dried, and recrystallized
from ethanol to give 11 as buff crystals. Yield: 0.156 g (58%);
mp 206–208ꢀC; 1H-NMR (400 MHz, DMSO-d6): d ¼ 6.32
(m, 1H, pyrrole H), 6.63 (m, 1H, pyrrole H), 6.98 (m, 1H, pyr-
role H), 7.20 (m, 3H, ArH), 7.71 (m, 2H, ArH), 8.15 (s, 1H,
pyrazole H), 11.80 (s, 1H, NH); IR (KBr): 3200 (NH), 1620
(C¼¼N), 1170 cmꢁ1 (C¼¼S); MS: m/z (%) ¼ 266 [Mþ] (57),
265 (7), 255 (11), 250 (10), 249 (51), 238 (39), 223 (57), 210
(13), 210 (13), 206 (34), 196 (40), 195 (33), 193 (52), 180
(36), 168 (45), 130 (35), 128 (28), 93 (20), 78 (12), 76 (100),
67 (66). Anal. Calcd. for C14H10N4S (266.32): C, 63.14; H,
3.78; N, 21.04. Found: C, 63.15; H, 3.72; N, 21.11.
Method B. A mixture of 1 (224 mg, 1 mmol) and P2S5 (442
mg, 2 mmol) in 10 mL of dry pyridine was heated under reflux
for 4 h. The solvent was removed under reduced pressure, and
the residue formed was diluted with water. The solid product
obtained was filtered off, dried, and recrystallized from ethanol
to give 11 as buff crystals. Yield 0.136 g (51%); mp 206–208ꢀC.
1-Phenyl-5-(4-nitrophenyl)-4,5-dihydro-1H-pyrazolo[4,3-e]-
pyrrolo[1,2-a]pyrazine (8e). This compound was obtained as
yellow crystals. Yield (57%); mp 256–258ꢀC; 1H-NMR (400
MHz, DMSO-d6): d ¼ 5.69 (s, 1H, pyrazine H), 5.75 (m, 1H, pyr-
role H), 6.12 (m, 1H, pyrrole H), 6.33 (m, 1H, pyrrole H), 7.53
(m, 5H, ArH), 7.68 (d, 2H, ArH, J ¼ 8.5 Hz), 8.21 (d, 2H, ArH,
J ¼ 8.5 Hz), 8.41 (s, 1H, pyrazole H), 8.57 (s, 1H, NH, D2O
exchangeable); IR (KBr): 3350 (NH), 1620, 1600 cmꢁ1 (C¼¼N);
MS: m/z (%) ¼ 358 (M þ 1) (12), 357(Mþ) (48), 356 (M ꢁ 1)
(35), 355 (M ꢁ 2) (100), 354 (5), 310 (7), 309 (14), 308 (6), 282
(7), 236 (17), 235 (76), 179 (8), 178 (5), 177 (4), 167 (11), 155
(6), 149 (34), 77 (19). Anal. Calcd. for C20H15N5O2 (357.37): C,
67.22; H, 4.23; N, 19.60. Found: C, 67.18; H, 4.21; N, 19.65.
General procedure for preparation of 1-phenyl-5-cycloal-
kanespiro-4,5-dihydro-1H-pyrazolo[4,3-e]pyrrolo[1,2-a]pyra-
zines (9a,b). A mixture of 7 (260 mg, 1 mmol) and the appro-
priate cyclic ketones (1 mmol) in 10 mL of absolute ethanol
was heated under reflux for 4 h. The reaction mixture was con-
centrated, and the solid product obtained on cooling was col-
lected by filtration and recrystallized from ethanol to give the
corresponding derivatives 9a,b.
REFERENCES AND NOTES
[1] Imaizumi, K.; Sado, T. Jpn. Kokai Tokkyo Koho 06-80,570
[9480 570] (Cl. AGlK31/495); Chem Abstr 1994, 121, 91797w.
[2] Sado, T.; Inoue, A. Jpn. Kokai Tokkyo Koho 02-101,078
[90 101 78] (Cl. C07D487/04); Chem Abstr 1990, 113, 78422k.
[3] Suzuki, S.; Inoue, A. Jpn. Kokai Tokkyo Koho 02-172,988
[90 172 9881] (Cl. C07D487/04); Chem Abstr 1990, 113, 218276t.
[4] Suzuki, S. Jpn. Kokai Tokkyo Koho 02-240,084 [90 240
84] (Cl. C07D487/04); Chem Abstr 1990, 114, 178382m.
[5] Hofmann, J.; Sickerand, D.; Mann, G. Ger. (East) 276,688
(Cl. CO7 D487/04); Chem Abstr 1990, 113, 231409h.
[6] Rangnekar, D. W.; Dhamnaskar, S. V. J Chem Technol
Biotechnol 1990, 49, 311.
1-Phenyl-1H,4H-pyrazolo[4,3-e]pyrrolo[1,2-a]pyrazine-5-
spirocyclopentane. This compound was obtained as buff crys-
1
tals. Yield (62%); mp 252–254ꢀC; H-NMR (400 MHz, DMSO-
d6): d ¼ 1.60 (m, 4H, cyclopentane H), 1.95 (m, 4H, cyclopen-
tane H), 6.00 (m, 1H, pyrrole H), 6.18 (m, 1H, pyrrole H), 6.87
(m, 1H, pyrrole H), 6.98 (m, 3H, ArH), 7.28 (m, 2H, ArH), 8.14
(s, 1H, pyrazole H), 8.27 (s, 1H, NH) IR (KBr): 3300 (NH),
1620 cmꢁ1 (C¼¼N). Anal. Calcd. for C18H18N4 (290.36): C,
74.46; H, 6.25; N, 19.30. Found: C, 74.51; H, 6.24; N, 119.28.
1-Phenyl-1H,4H-pyrazolo[4,3-e]pyrrolo[1,2-a]pyrazine-5-
spirocyclopentane. This compound was obtained as buff crys-
[7] Suzuki, S.; Suzuki, K.; Honda, H. Ger. Offen. 3, 237: 243;
Chem Abstr 1984, 100, 68319z.
ˇ
[8] Svetlik, J. Heterocycles 1984, 22, 2513.
1
tals. Yield (42%); mp 248–250ꢀC; H-NMR (400 MHz, DMSO-
d6): d ¼ 1.20 (m, 4H, cyclohexane H), 1.76 (m, 6H, cyclohexane
H), 6.05 (m, 1H, pyrrole H), 6.28 (m, 1H, pyrrole H), 6.89 (m,
1H, pyrrole H), 7.00 (m, 3H, ArH), 7.29 (m, 2H, ArH), 8.12 (s,
1H, pyrazole H), 8.29 (s, 1H, NH); IR (KBr): 3220 (NH), 1620
cmꢁ1 (C¼¼N). Anal. Calcd. for C19H20N4 (304.39): C, 74.97; H,
6.62; N, 18.41. Found: C, 75.02; H, 6.55; N, 18.31.
[9] El-Emary, T. I.; Kamal El-Dean, A. M.; El-Kashef, H. S.
Farmaco 1998, 53, 383.
[10] El-Kashef, H. S.; El-Emary, T. I.; Gasquet, M.; Timon-
David, P.; Maldonado, J.; Vanelle, P. Pharmazie 2000, 55, 572.
[11] Stefancich, G.; Corelli, F.; Massa, S.; Silvestri, R.; Di
Santo, R. J Heterocycl Chem 1987, 24, 1199.
1-Phenyl-4,5-dihydro-1H-pyrazolo[4,3-e]pyrrolo[1,2-a]pyra-
zin-5-one (10). A mixture of 1 (224 mg, 1 mmol) and (162 mg,
1 mmol) of CDI in 10 mL of dioxane was heated under reflux
for 6 h. The solvent was removed under reduced pressure, and the
residue obtained was triturated with water. The solid product formed
was filtered off, dried, and recrystallized from ethanol to afford 10
as white crystals. Yield: 0.210 g (84%); mp 296–298ꢀC (ref. 9,
[12] Massa, S.; Stefancich, G.; Artico, M.; Corelli, F.; Ortenzi,
G. Heterocycles 1985, 23, 1417.
[13] Farghaly, A.; El-Kashef, H. Monatsh Chem 2005, 136, 217.
[14] Kopp, M.; Lancelot, J-C.; Dallemagne, P.; Rault, S. J Het-
erocycl Chem 2001, 38, 1045
´
[15] de Sevricourt, M.; El-Kashef, H.; Rault, S.; Robba, M. Syn-
thesis 1981, 9, 710.
1
297–298ꢀC, 53%); H-NMR (400 MHz, DMSO-d6): d ¼ 6.36 (m,
[16] El-Kashef, H.; Rault, S.; Lancelot, J. C.; Robba, M. J Het-
erocycl Chem 1986, 23, 161.
1H, pyrrole H), 6.68 (m, 1H, pyrrole H), 6.94 (m, 1H, pyrrole H),
7.22 (m, 3H, ArH), 7.78 (m, 2H, ArH), 8.18 (s, 1H, pyrazole H),
11.50 (s, 1H, NH); IR (KBr): 3380 (NH), 1690 (C¼¼O), 1620 cmꢁ1
(C¼¼N); MS: m/z (%) ¼ 250 [Mþ] (75), 223 (100), 206 (15), 195
(66), 180 (19), 168 (91), 130 (24), 128 (20), 93 (19), 87 (20), 78
(18), 76 (92), 66 (49). Anal. Calcd. for C14H10N4O (250.26): C,
67.19; H, 4.03; N, 22.39. Found: C, 67.26; H, 4.09; N, 22.42.
1-Phenyl-4,5-dihydro-1H-pyrazolo[4,3-e]pyrrolo[1,2-a]pyraz-
[17] Radwan, S.; Abbady, M. S.; El-Kashef, H. S. Phosphorus
Sulfur Silicon Relat Elem 1994, 89, 193.
[18] El-Kashef, H. S.; Kamal El-Dean, A. M.; Geies, A. A.; Lance-
lot, J. C.; Dallemagne, P.; Rault, S. J Heterocycl Chem 2000, 37, 1521.
[19] Bakhite, E. A.; Geies, A. A.; Kamal El-Dean, A. M.; El-
Kashef, H. S. Phosphorous Sulfur Silicon Relat Elem 1995, 104, 143.
[20] Weinstock, J. J Org Chem 1961, 26, 3511.
ine-5-thione (11). Method A. A mixture of 1 (224 mg, 1
mmol) and 3 mL of CS2 in 10 mL of dry pyridine was heated
[21] Farghaly, A.; El-Kashef, H. ARKIVOC 2006, (xi), 76.
[22] Farghaly, A.; El-Kashef, H. Monatsh Chem 2006, 137, 1195.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet