3898 Al-Tilasi et al.
Asian J. Chem.
[M+] (62) (C19H21N5O), 291 [M-CONH2] (80),252 [M-2C2H4-
HCN] (43), 222 [252-C2H4-2H] (26), 91 [C6H5N+] (38), 77
[C6H5+] (100), 51 [77-C2H2] (64).
12.0,3J9ax-8ax = 6.0,3J9ax-8eq = 3.7,Heq-9), 3.45 (1H, t, J = 5.8, H-
5a), 3.57 [1H, d, 2J4ax-4eq = 15.4, Hax-4, (A part ofAB system)],
2
3.72 [1H, d, J4ax-4eq = 15.4, Heq-4, (B part of AB system)],
2-Cyano-3-(1-phenyl-3-propyl-5-pyrrolidino-1H-
pyrazol-4-yl)prop-2-enethioamide (5e): Fine orange cubes,
m.p. 176-177°C;Yield 76%; IR (KBr, νmax, cm-1): 2204 (CN),
1645 (C=C), 1509 (C=S), 3289, 3334 (NH2);1H NMR (CDCl3):
0.96 (3H, t, J = 7.3, CH3), 1.69 (2H, sext, J = 7.3, CH2), 2.75
(2H, t, J = 7.3, CH2), 1.80-1.85 (4H, m, 2CH2 of the pyrrolidino
group), 3.21-3.26 (4H, m, CH2-N-CH2), 7.58 (2H, br. s,
NH2),7.38-7.48 (5H, m,Ar-H), 8.95 (1H,s, H-C=C); 13C NMR:
13.7 (CH3), 21.5 (CH2), 30.5 (CH2), 25.4, 51.1 (pyrrolidinogroup
carbons),101.2, 104.5, 125.5, 128.0, 128.8, 139.6, 150.2,
151.8, 153.6 (sp2 carbons), 116.8 (CN), 193.0 (C=S); MS:
m/z (%) 365 [M+] (25) (C20H23N5S), 332 [M-NH2-CH3-2H]
(37), 303 [M-CSNH2-2H] (78), 266 [M-2C2H4-C3H7] (23), 91
[C6H5N+] (21), 77 [C6H5+] (100), 51 [77-C2H2] (48).
3.67-3.77 (2H, m, H2-8), 4.26 (2H, d, J = 5.1, H2-6), 7.35-
7.51 (6H, m, H-3',3'’,4',4'’,5'.5'’), 7.65 (4H, d, J = 7.0, H-
13
2',2'’,6',6'’); C NMR: 32.8 (C-4), 59.0 (C-5a), 66.4 (C-6),
65.1 (C-8), 46.4 (C-9), 112.9, 113.4 (CN), 30.5, 94.5, 144.1,
148.3 (C-5,3a,10a,3),122.9, 126.1, 127.2, 127.7, 128.1, 128.8,
131.4, 138.8 (phenyl group carbons); MS: m/z (%) 381 [M+]
(60) (C23H19N5O), 352 [M-HCN-2H] (11), 324 [352-HCN-H]
(4), 316 [M-C3N2-H] (6), 260 [M-C2H4O-C6H5] (5), 91
[C6H5N+] (10), 77 [C6H5+] (100), 51 [77-C2H2] (46).
1,3-Diphenyl-1,4,6,7,8,9-hexahydropyrazolo[4,3-
c]quinolizine-5,5(5aH)-dicarbonitrile (6c): White powder,
m.p. 209-210°C;Yield 21 %; IR (KBr, νmax, cm-1): 2253 (CN);
1H NMR (CDCl3): 1.54 (3H, br. peak, H2-7,Hax-8),1.86-2.05
[2H, m, Hax-6, (A part of ABX system) and Heq-8], 2.33 [1H,
d, 2J6ax-6eq = 12.4, Heq-6, (B part of ABX system)], 2.47-2.55
(1H, m, Hax-9), 3.28 [1H, dd, 3J5aax-6ax = 9.0, 3J5aax-6eq = 2.5, H-
5a, (X part ofABX system)], 3.43 (1H, d, 2J9ax-9eq = 11.5, Heq-9),
Synthesis of 3-substituted 1-phenyl-1,4,5a,6,8,9-
hexahydro-5H-pyrazolo[4',3':5,6]pyrido[2,1-c][1,4]-
oxazine-5,5-dicarbonitrile (6a,b); 1,3-diphenyl-1,4,6,7,8,9-
hexahydropyrazolo[4,3-c]quinolizine-5,5(5aH)-
dicarbonitrile (6c); 5-cyano-3-ethyl-1-phenyl-4,5,5a,6,7,8-
hexahydro-1H-pyrazolo[3,4-e]indolizine-5-carboxamide
(6d) and 5-cyano-1-phenyl-3-propyl-4,5,5a,6,7,8-hexahydro-
1H-pyrazolo[3,4-e]indolizine-5-carbothioamide (6e): A
mixture of 5a-e (2.5 mmol) in dry toluene (15 mL) was added
anhydrous zinc chloride (2.5 mmol) and the resulted mixture
was refluxed for 7-17 h under anhydrous conditions. After
completion, (monitored by TLC) the reaction mixture was
cooled, water was added and extracted with dichloromethane
(3 × 20 mL). The combined organic phases were dried over
anhydrous sodium sulfate overnight and concentrated in vacuo.
Evaporation of the solvent followed by column chromato-
graphy gave pure 6a-e. The compound 6c was recrystallized
from benzene/petroleum ether 60-80°C25.
2
3.53 [1H, d, J4ax-4eq = 15.1, Hax-4, (A part of AB system)],
2
3.61 [1H, d, J4ax-4eq = 15.1, Heq-4, (B part of AB system)],
7.33-7.50 (6H, m, H-3',3'’,4',4'’,5'.5'’), 7.62 (4H, d, J = 7.0,
H-2',2'’,6',6'’); 13C NMR: 32.2 (C-4), 62.6 (C-5a), 23.3 (C-6),
22.3 (C-7), 27.5 (C-8), 49.7 (C-9), 112.7, 113.9 (CN), 36.6,
93.9, 145.0, 148.6 (C-5,3a,10a,3),123.1, 126.4, 127.2, 127.7,
128.1, 128.7, 131.6, 139.6 (phenyl group carbons); MS: m/z
(%) 379 [M+] (100) (C24H21N5), 351 [M-HCN-H] (10), 325
[M-2HCN] (5), 314 [M-C3N2-H] (37), 246 [M-2C2H4-C6H5]
(16),115 [M-C7H5N-C9H11N3] (23), 91 [C6H5N+] (12), 77 [C6H5+]
(92), 51 [77-C2H2] (52).
5-Cyano-3-ethyl-1-phenyl-4,5,5a,6,7,8-hexahydro-1H-
pyrazolo[3,4-e]indolizine-5-carboxamide (6d): Yellow
scales, m.p. 204-206 °C; Yield 31 %; IR (KBr, νmax, cm-1):
2229 (CN), 1692 (C=O), 3305, 3386 (NH2); 1H NMR (CDCl3):
0.83 (3H, t, J = 8.1, CH3), 2.61 (2H, quint, J = 8.1, CH2), 1.86-
2.11 (3H, m, Hax-6, H2-7), 2.32-2.37 (1H, m, Heq-6), 2.91-3.00
(1H, m, Hax-8), 3.07-3.20 (3H, m, H2-4, Heq-8), 3.97 (1H, dd,
3J5aax-6ax = 7.7, 3J5aax-6eq = 4.4, H-5a), 5.80 and 6.53 (1H, br. s
and1H, br. s, D2O exchangeable, NH2), 7.29 (1H, t, J = 7.9, H-
4'), 7.41 (2H, t, J = 7.9, H-3',5'),7.53 (2H, d, J = 7.9, H-2',6');
13C NMR: 12.3 (CH3), 21.7 (CH2),36.1 (C-4), 63.4 (C-5a),
22.9 (C-6), 27.0 (C-7), 43.3 (C-8), 48.9, 93.8, 143.0, 150.9
(C-5,3a,9a,3),123.3, 126.0, 128.0,138.8 (phenyl group
carbons), 119.2 (CN),168.1 (C=O); MS: m/z (%) 335 [M+]
(62) (C19H21N5O), 291 [M-CONH2] (96), 252 [M-2C2H4-HCN]
(12), 248 [291-C2H4-CH3] (13),91 [C6H5N+] (17), 77 [C6H5+]
(100), 51 [77-C2H2] (47).
3-Methyl-1-phenyl-1,4,5a,6,8,9-hexahydro-5H-
pyrazolo[4',3':5,6]pyrido[2,1-c][1,4]oxazine-5,5-
dicarbonitrile (6a): Pale beige cubes, m.p. 151-152°C;Yield
36 %; IR (KBr, νmax, cm-1): 2243 (CN);1H NMR (CDCl3): 2.21
(3H, s,CH3), 2.73 (1H, ddd,2J9ax-9eq = 12.1,3J9ax-8ax = 6.8,3J9ax-8eq
= 3.4, Hax-9), 3.31-3.37[2H, m, H-5a, (X part of ABX system)
2
and Heq-9], 3.26[1H, d, J4ax-4eq = 15.4, Hax-4, (A part of AB
2
system)], 3.46 [1H, d, J4ax-4eq = 15.4, Heq-4, (B part of AB
system)], 3.62-3.76 (2H, m, H2-8), 4.17 [1H, dd,2J6ax-6eq
=
13.5,3J5aax-6ax = 5.9,Hax-6, (A part of ABX system)], 4.24 [1H,
dd,2J6ax-6eq = 13.5,3J5aax-6eq = 3.3,Heq-6, (B part ofABX system)],
7.32 (1H, t, J = 7.3, H-4'), 7.43 (2H, t, J = 7.3, H-3',5'),7.55
13
(2H, d, J = 7.3, H-2',6'); C NMR: 11.1 (CH3), 31.2 (C-4),
59.0 (C-5a), 66.2 (C-6), 65.0 (C-8), 46.3 (C-9), 112.4, 113.2
(CN), 30.3, 95.1, 143.3, 145.7 (C-5,3a,10a,3),122.5, 126.8,
128.5, 138.6 (phenyl carbons); MS: m/z (%) 319 [M+] (100)
(C18H17N5O), 290 [M-HCN-2H] (16), 262 [290-HCN-H] (29),
254 [M-C3N2-H] (26), 198 [M-C2H4O-C6H5] (31), 91 [C6H5N+]
(26), 77 [C6H5+] (87), 51 [77-C2H2] (62).
5-Cyano-1-phenyl-3-propyl-4,5,5a,6,7,8-hexahydro-
1H-pyrazolo[3,4-e]indolizine-5-carbothioamide (6e):
Orange cubes, m.p. 186 °C; Yield 46%; IR (KBr, νmax, cm-1):
2234 (CN), 1526 (C=S), 3358, 3423 (NH2); 1H NMR (CDCl3):
0.97 (3H, t, J = 7.3, CH3), 1.67 (2H, sext, J = 7.3, CH2), 2.55
(2H, t, J = 7.3, CH2), 1.81-1.94 (2H, m, Hax-6, Hax-7), 2.01-
2.06 (1H, m, Heq-7), 2.27-2.38 (1H, m, Heq-6), 2.93-3.02 (1H,
1,3-Diphenyl-1,4,5a,6,8,9-hexahydro-5H-pyrazolo-
[4',3':5,6]pyrido[2,1-c][1,4]oxazine-5,5-dicarbonitrile (6b):
2
m, Hax-8), 3.05 [1H, d, J4ax-4eq = 15.4, Hax-4, (A part of AB
system)], 3.17-3.23 (1H, m, Heq-8), 3.49[1H, d, 2J4ax-4eq = 15.4,
3
Heq-4, (B part of AB system)], 4.22 (1H, dd, J5aax-6ax = 6.0,
3J5aax-6eq = 4.8, H-5a), 7.28 (1H, t, J = 7.6, H-4'), 7.41 (2H, t,
Pale yellow cubes, m.p. 266-267°C;Yield 39 %; IR (KBr, νmax
,
cm-1): 2248 (CN); 1H NMR (CDCl3): 2.79 (1H, ddd, 2J9ax-9eq
12.0,3J9ax-8ax = 6.0,3J9ax-8eq = 3.3,Hax-9), 3.40 (1H, ddd, 2J9ax-9eq
=
=