May-Jun 2001
Synthesis of Pyrazole-fused Azepino[5,4,3-cd]indoles
627
111 (32); hrms: Calcd for C
H
N O Cl: 394.11965. Found:
Anal. Calcd. for C H N (312.37): C, 76.90; H, 5.16; N,
20 16 4
17.94. Found: C, 77.03; H, 5.24; N, 17.65.
The following azepino[5,4,3-cd]indoles were prepared via the
cyclization of the appropriate amide (9) using phosphorous oxy-
chloride and following the same above procedure and experimen-
tal conditions.
21 19
4
2
1
394.12203; H nmr (400.14 MHz, DMSO-d ): δ 2.07 (s, 3H, C3'-
6
CH ), 3.59 (s, 3H, N-CH ), 3.72 (s, 3H, OCH ), 6.72 (dd, 1H, J =
3
3
3
8.8, 2.4 Hz, H-6), 6.84 (d, 1H, J = 2.4 Hz, H-4), 7.30 (d, 1H, J =
8.8 Hz, H-7), 7.54 (d, 1H, J = 2.7 Hz,H-2), [p-C H Cl : 7.51(d,
2H, J = 8.5 Hz, H-3''/H-5''), 7.87(d, 2H, J = 8.5 Hz, H-2''/H-6'')],
9.57 (s, 1H, NHCO), 11.41 (broad s, 1H, N-H); C nmr (100.62
6
4
13
5-(4-Chlorophenyl)-6-methoxy-1,3-dimethylpyrazolo[3',4':6,7]-
azepino[5,4,3-cd]indole (10b).
MHz, DMSO-d ): δ 11.5 (C3'-CH ), 37.1 (N-CH ), 55.0
6
3
3
(OCH ), 100.3 (C-4), 102.7 (C-3), 112.3 (C-7), 112.6 (C-6),
3
This compound was prepared from compound (9b) (1.18 g; 3
mmol) and phosphorous oxychloride (8 mL); Yield of 10b = 0.85 g
(75%); mp 267-269 °C (dec.); ms: m/z (% rel. int.): 376 (M ,
100), 361 (21), 326 (15), 304 (9), 284 (14), 270 (17), 254 (6), 215
115.5 (C-4'), 126.2 (C-3a), 126.3 (C-2), 128.3 (C-3''/C-5''), 129.4
(C-2''/C-6''), 130.9 (C-5'), 133.0 (C-7a), 133.8(C-1''),
136.2(C-4''), 143.7 (C-3'), 153.8 (C-5), 165.3 (NHCO).
.
+
Anal. Calcd. for C
H N O Cl (394.86): C, 63.88; H, 4.85;
21 19 4 2
(7), 188 (24), 155 (18), 115 (21); hrms: Calcd for C H N OCl:
N, 14.19; Cl, 8.98. Found: C, 64.07; H, 5.12; N, 14.01; Cl, 8.92.
21 17 4
1
376.10779. Found: 376.10909; H nmr (400.12 MHz, DMSO-d ):
6
3-[4-(2-Thenoyl)amino-1,3-dimethylpyrazol-5-yl]indole (9c).
δ 2.03 (s, 3H, C3-CH ), 3.19 (s, 3H, N-CH ), 3.77 (s, 3H, OCH ),
3
3
3
6.77 (d, 1H, J = 8.2 Hz, H-7), 7.21 (d, 1H, J = 8.2 Hz, H-8), 7.24 (d,
This compound was prepared from 2-thiophenecarbonyl chlo-
2H, J = 8.4 Hz, H-2''/H-6''), 7.31 (d, 2H, J = 8.4 Hz, H-3''/H-5'')
ride (0.81 g; 5.5 mmol) and (8a) (1.13 g; 5.0 mmol); Yield of 9c =
13
.
+
7.44 (br d, 1H, J = 2.7 Hz, H-10), 11.33 (broad s, 1H, N-H);
C
1.25 g (74%); mp 217 - 220 °C; ms: m/z (% rel. int.): 336 (M ,
47), 225 (100), 157 (41), 142 (33), 115(9), 111 (33); hrms: Calcd
nmr (100.62 MHz, DMSO-d ): δ 10.1 (C3-CH ), 38.7 (N-CH ),
6
3
3
1
55.1 (OCH ), 107.7 (C-10a), 111.9 (C-7), 115.0 (C-8), 117.2 (C-
for C H N OS: 336.10448. Found: 336.10614; H nmr (400.12
3
18 16
4
5a), 120.0 (C-10), 126.1 (C-8b), 127.1 (C-2''/C-6''), 127.7 (C-3''/C-
5''), 131.0 (C-10b), 131.1 (C-3), 132.8(C-4''), 132.9 (C-8a),
145.2(C-1''), 146.0 (C-3a), 152.1 (C-6), 155.8 (C-5).
MHz, DMSO-d ): δ 2.08 (s, 3H, C3'-CH ), 3.70 (s, 3H, N-CH ),
6
3
3
6.99 (ddd, 1H, J~ 8.0, 8.0, 0.7 Hz, H-5), 7.09 (dd, 1H, J = 4.9, 3.6
Hz, H-3''), 7.11 (m, 1H, H-6), 7.43 (dd overlapped, 2H, J~ 8.0 Hz,
H-4 and H-7), 7.54 (d, 1H, J = 2.4 Hz, H-2), 7.74 (dd, 1H, J = 4.9,
1.1 Hz, H-4''). 7.77(dd, 1H, J = 1.1, 3.6 Hz, H-5''), 9.48 (s, 1H,
Anal. Calcd. for C
H N OCl (376.85): C, 66.93; H, 4.55; N,
21 17 4
14.87; Cl, 9.41. Found: C, 66.74; H, 4.38; N, 14.65; Cl, 9.28.
13
NHCO), 11.50 (broad s, 1H, N-H); C nmr (100.62 MHz,
1,3-Dimethyl-5-(2-thienyl)pyrazolo[3',4':6,7]azepino[5,4,3-cd]-
indole (10c).
DMSO-d ): δ 11.4 (C3'-CH ), 37.2 (N-CH ), 102.8 (C-3), 111.9
6
3
3
(C-7), 115.1 (C-4'), 119.2 (C-4), 119.6 (C-5), 121.6 (C-6), 125.8
(C-3a), 126.0 (C-2), 127.9 (C-4''), 128.6 (C-5''), 131.1(C-3''), 134.2
(C-5'), 136.0 (C-7a), 139.7 (C-2''), 143.8 (C-3'), 161.2 (NHCO).
This compound was prepared from compound (9c) (0.84 g; 2.5
mmol) and phosphorous oxychloride (7 mL); Yield of 10c = 0.35
.
+
g (44%); mp 224-225 °C (dec.); ms: m/z (% rel. int.): 318 (M ,
100), 276 (16), 262 (26), 235 (19), 232 (9), 164 (7), 159 (14), 125
Anal. Calcd. for C
H N OS (336.42): C, 64.27; H, 4.79; N,
18 16 4
16.65, S, 9.53. Found: C, 64.44; H, 4.82; N, 16.31, S, 9.52.
(6); hrms: Calcd for C
H N S: 318.0939. Found: 318.093321;
18 14 4
1
1,3-Dimethyl-5-phenylpyrazolo[3',4':6,7]azepino[5,4,3-cd]-
indole (10a).
H nmr (400.12 MHz, DMSO-d ): δ 2.01 (s, 3H, C3-CH ), 3.82
6
3
(s, 3H, N-CH ), 6.91 (dd, 1H, J = 8.0, 8.2 Hz, H-7), 7.03 (dd, 1H,
3
J = 5.0, 3.2 Hz, H-4''), 7.07 (d, 1H, J = 8.0 Hz, H-6), 7.18 (d, 1H,
J = 8.2 Hz, H-8), 7.33 (dd, 1H, J = 3.2, 1.0 Hz, H-3''), 7.45(d, 1H,
J = 2.7 Hz, H-10), 7.51 (dd, 1H, J = 5.0, 1.0 Hz, H-5''), 11.46
To a stirred solution of compound (9a) (0.86 g; 2.6 mmol) in
acetonitrile (30mL) was added phosphorous oxychloride (7 mL).
The resulting mixture was refluxed (oil bath, 110 °C) for 6 hours
under continuous stirring. Excess acetonitrile and phosphorous
oxychloride were removed under vacuum and the residue was
poured onto ice-cooled water (100 mL). The cold aqueous solution
was basified with 10% NaOH solution and extracted with
dichloromethane (3x100 mL). The combined organic extracts were
13
(broad s, 1H, N-H); C nmr (100.62 MHz, DMSO-d ): δ 10.1
6
(C3-CH ), 39.0 (N-CH ), 107.7 (C-10a), 114.4 (C-8), 118.7
3
3
(C-10), 121.4 (C-7), 123.0 (C-6), 126.1 (C-3''), 126.4 (C-4''),
126.6 (C-5''), 129.6 (C-8b), 129.9 (C-5a), 130.5 (C-3), 130.6
(C-10b), 137.6 (C-8a), 147.0 (C-3a), 147.3 (C-2''), 150.7 (C-5).
Anal. Calcd. for C
H N S (318.40): C, 67.90; H, 4.43; N,
18 14 4
dried (anhydrous MgSO ), and upon evaporation of the CH Cl ,
4
2
2
17.60, S, 10.07. Found : C, 67.70; H, 4.32; N, 17.46, S, 10.03.
gave a crude orange solid. Yield 0.63 g (78%). The product was
further purified on silica gel TLC plates, eluting with
Acknowledgements.
CH Cl :MeOH (97:3 v/v) to afford the title compound in analyti-
2
2
We are grateful to the BMBF, Bonn, Germany and the
University of Sharjah, U A E, for financial support. K. A. S.
wishes to thank the Hashemite University, Zarqa, Jordan for the
scholarship.
cally pure form. Yield of 10a = 0.41 g (50%); mp 255-257 °C; ms:
.
+
m/z (% rel. int.): 312 (M , 100), 270 (24), 256 (9), 229 (45), 201
(9), 175 (6), 156 (32), 148 (21), 134 (15), 107 (16), 101 (12);
1
hrms: Calcd for C H N : 312.13748. Found: 312.138158; H
20 16
4
nmr (400.12 MHz, DMSO-d ): δ 1.95 (s, 3H, C3-CH ), 3.84 (s,
6
3
3H, N-CH ), 6.33 (d, 1H, J = 8.0 Hz, H-6), 6.78 (dd, 1H, J = 8.1,
REFERENCES AND NOTES
3
8.0 Hz, H-7), 7.11 (d, 1H, J = 8.1Hz, H-8), 7.37 (m, 5H, C H ),
6
5
13
7.44 (d, 1H, J = 2.4 Hz, H-10), 11.43 (broad s, 1H, N-H); C nmr
(100.62 MHz, DMSO-d ): δ 10.2 (C3-CH ), 39.1 (N-CH ), 107.9
[*] E-mail: mustelab@ ju.edu.jo
[†] On leave from the University of Jordan.
6
3
3
(C-10a), 114.0 (C-8), 118.3 (C-10), 122.5 (C-7), 122.9 (C-6), 126.5
(C-8b), 127.6 (C-4''), 127.8 (C-2''/ C-6''), 128.1 (C-3''/C-5''), 129.6
(C-5a), 130.6 (C-10b), 131.0 (C-3), 137.4 (C-8a), 143.3 (C-1'),
147.4 (C-3a), 157.8 (C-5).
[1a] G. S. King, P. G. Mantle, C. A. Szczyrbak and E. S.
Waight, Tetrahedron Lett., 215 (1973); [b] G. S. King, E. S. Waight,
P. G. Mantle and C. A. Szczyrbak, J. Chem. Soc. Perkin Trans. I,
2099 (1977).