236
E. Yamuna et al. / European Journal of Medicinal Chemistry 47 (2012) 228e238
(63%); IR (KBr, cmꢀ1
500 MHz) (ppm) d: 2.00 (s, 3H, C10eCH3), 2.11e2.17 (m, 2H, C5e2H),
)
nmax: 3233, 2922, 1590; 1H NMR (CDCl3,
(C12a), 134.56 (C11a), 140.37 (C4), 159.17 (C2); MS: m/z (%) 265 (100)
[Mþ]; Anal. Calcd. for: C16H15N3O: C, 72.43; H, 5.70; N,15.84. Found:
C, 72.40; H, 5.74; N, 15.89%.
2.93e2.96 (m, 2H, C4e2H), 3.14e3.17 (m, 2H, C6e2H), 6.89 (d, 1H,
C9eH, J ¼ 8.00 Hz), 6.99 (t, 1H, C8eH, J ¼ 8.00 Hz), 7.07 (b s, 1H,
N
11eH), 7.36 (d,1H, C7eH, J ¼ 8.00 Hz), 7.50 (s, 1H, C3eH), 7.55e7.61
6.1.5.2. 2-Hydroxy-10-methyl-5,6,7,12-tetrahydropyrimido[50,60:6,7]
(m, 5H, C2 -, C3 -, C4 -, C5 - & C6 -H); 13C NMR (CDCl3, 125 MHz)
(ppm) : 15.55 (C10eCH3), 24.16 (C4), 25.88 (C5), 26.43 (C6), 116.29
cyclohepta[b]indole (6b). Yellow solid; M.p. 246 ꢁC; Yield: 0.188 g
0
0
0
0
0
d
(71%); IR (KBr, cmꢀ1 nmax: 3437, 3263, 1608; 1H NMR (CDCl3,
)
(C7), 116.46 (C6a), 119.61 (C3a), 120.00 (C9), 121.67 (C11b), 123.31 (C8)0,
500 MHz) (ppm) d: 2.10e2.13 (m, 2H, C6e2H), 2.44 (s, 3H, C10eCH3),
0
0
0
123.35 (C10), 127.35 (C2 & C6 ), 127.57 (C6b), 129.48 (C4 ), 129.64 (C3
2.90e2.92 (m, 2H, C5e2H), 3.12e3.14 (m, 2H, C7e2H), 6.98 (d, 1H,
C9eH, J ¼ 8.00 Hz), 7.04 (s, 1H, C11eH), 7.39 (d, 1H, C8eH,
J ¼ 8.00 Hz), 7.49 (s, 1H, C4eH), 9.21 (b s, 1H, N12eH), 11.34 (s,1H, C2-
0
0
& C5 ), 133.43 (C11a), 134.82 (C10a), 140.59 (C3), 140.91 (C1 ); MS: m/z
(%) 313 (100) [Mþ]; Anal. Calcd. for: C21H19N3: C, 80.48; H, 6.11; N,
13.41. Found: C, 80.43; H, 6.14; N, 13.43%.
OH); 13C NMR (CDCl3, 125 MHz) (ppm)
d: 21.39 (C10eCH3), 24.25
(C5), 25.43 (C6), 26.41 (C7), 111.28 (C11), 116.24 (C7a), 118.71 (C8),
119.18 (C4a), 121.48 (C9), 126.86 (C12b), 127.31 (C7b), 128.51 (C9),
133.48 (C12a), 134.68 (C11a), 140.44 (C4), 158.98 (C2); MS: m/z (%) 265
(100) [Mþ]; Anal. Calcd. for: C16H15N3O: C, 72.43; H, 5.70; N, 15.84.
Found: C, 72.43; H, 5.75; N, 15.80%.
6.1.4.4. 1-Phenyl-4,5,6,11-tetrahydro pyrazolo[40,30:6,7]cyclohepta[b]
indole (5d). Yellow solid; M.p. 243 ꢁC; Yield: 0.188 g (63%); IR (KBr,
cmꢀ1 nmax: 3234, 2925, 1592; 1H NMR (CDCl3, 500 MHz) (ppm)
) d:
2.12e2.19 (m, 2H, C5e2H), 2.90e2.93 (m, 2H, C4e2H), 3.14e3.17 (m,
2H, C6e2H), 6.88 (d t,1H, C8eH, Jo ¼ 8.50 Hz, Jm ¼ 2.00 Hz), 6.99 (d t,
1H, C9eH, Jo ¼ 8.50 Hz, Jm ¼ 2.00 Hz), 7.09 (d, 1H, C10eH,
J ¼ 8.50 Hz), 7.15 (b s, 1H, N11eH), 7.39 (d, 01H, C7eH, J ¼ 8.50 Hz),
6.1.5.3. 2-Hydroxy-11-methyl-5,6,7,12-tetrahydropyrimido[50,60:6,7]
cyclohepta[b]indole (6c). Yellow solid; M.p. 213 ꢁC; Yield: 0.193 g
7.49 (s,1H, C3eH), 7.55e7.60 (m, 5H, C2 -, C3 -, C4 -, C5 - & C6 -H); 13C
(73%); IR (KBr, cmꢀ1 nmax: 3429, 3336, 1603; 1H NMR (CDCl3,
)
0
0
0
0
NMR (CDCl3, 125 MHz) (ppm)
d
: 24.17 (C4), 25.76 (C5), 26.31 (C6),
500 MHz) d: 2.09e2.13 (m, 2H, C6e2H), 2.48 (s, 3H, C11eCH3),
111.28 (C10),116.38 (C6a), 118.38 (C7),119.63 (C3a), 120.48 (C8),121.58
2.90e2.93 (m, 2H, C5e2H), 3.08e3.10 (m, 2H, C7e2H), 7.11 (t, 1H,
C9eH, J ¼ 8.00 Hz), 7.21 (d, 1H, C10eH, J ¼ 8.00 Hz), 7.41 (d, 1H,
C8eH, J ¼ 8.00 Hz), 7.48 (s, 1H, C4eH), 9.26 (bs, 1H, N12eH), 11.36
0
0
0
(C9)0 , 121.66 (C11b), 127.21 (C6b), 127.28 (C2 & C6 ), 129.50 (C4 ), 0129.87
0
(C3 & C5 ), 133.18 (C11a), 134.12 (C10a), 140.32 (C3), 140.79 (C1 ); MS:
m/z (%) 299 (100) [Mþ]; Anal. Calcd. for: C20H17N3: C, 80.24; H, 5.72;
(s,1H, C2-OH); 13C NMR (CDCl3, 125 MHz) (ppm)
d: 16.55 (C11eCH3),
N, 14.04. Found: C, 80.28; H, 5.76; N, 14.07%.
24.16 (C5), 25.88 (C6), 26.43 (C7), 116.29 (C7a), 116.46 (C8), 119.68
(C4a), 120.88 (C10), 123.35 (C9), 123.64 (C11), 126.48 (C12b), 127.58
(C7b), 133.41 (C12a), 134.12 (C11a), 140.91 (C4), 159.31 (C2); MS: m/z
(%) 265 (100) [Mþ]; Anal. Calcd. for: C16H15N3O: C, 72.43; H, 5.70; N,
15.84. Found: C, 72.48; H, 5.73; N, 15.87%.
6.1.4.5. 8-Chloro-1-phenyl-4,5,6,11-tetrahydro
cyclohepta[b]indole (5e). Yellow solid; M.p. 234 ꢁC; Yield: 0.233 g
(70%); IR (KBr, cmꢀ1 nmax: 3237, 2924, 1595; 1H NMR (CDCl3,
500 MHz) (ppm) : 2.11e2.17 (m, 2H, C5e2H), 2.92e2.94 (m, 2H,
pyrazolo[40,30:6,7]
)
d
C4e2H), 3.10e3.13 (m, 2H, C6e2H), 6.89 (d, 1H, C10eH, J ¼ 8.00 Hz),
7.05 (d d, 1H, C9eH, Jo ¼ 8.00 Hz, Jm ¼ 2.00 Hz), 7.18 (b s, 1H, N11eH),
7.48 (d, 1H0, C7eH, Jm ¼ 2.00 Hz), 7.52 (s, 1H, C3eH), 7.55e7.56 (m,
6.1.5.4. 2-Hydroxy-5,6,7,12-tetrahydropyrimido[50,60:6,7]cyclohepta
[b]indole (6d). Yellow solid; M.p. 189 ꢁC; Yield: 0.188 g (75%); IR
(KBr, cmꢀ1 nmax: 3432, 3262,1605; 1H NMR (CDCl3, 500 MHz) (ppm)
)
5H, C2 -, C3 -, C4 -, C5 - & C6 -H); 13C NMR (CDCl3, 125 MHz) (ppm)
d:
d: 2.08e2.13 (m, 2H, C6e2H), 2.91e2.93 (m, 2H, C5e2H), 3.09e3.11
0
0
0
0
24.54 (C4), 25.81 (C5), 26.41 (C6), 112.28 (C10), 116.23 (C6a), 119.54
(m, 2H, C7e2H), 7.04 (d t, 1H, C9eH, Jo ¼ 8.50 Hz, Jm ¼ 2.00 Hz), 7.21
(d t, 1H, C10eH, Jo ¼ 8.50 Hz, Jm ¼ 2.00 Hz), 7.26 (d, 1H, C11eH,
J ¼ 8.50 Hz), 7.40 (d,1H, C8eH, J ¼ 8.50 Hz), 7.45 (s,1H, C4eH), 9.24 (b
s, 1H, N12eH), 11.32 (s, 1H, C2-OH); 13C NMR (CDCl3, 125 MHz) (ppm)
0
(C3a), 120.11 (C7), 121.70 (C11b), 123.41 (C9), 126.98 (C6b), 127.37 (C2
0
0
0
0
& C6 ), 128.58 (C8), 129.31 (C4 ), 129.63 (C3 & C5 ), 133.11 (C11þa),
0
133.99 (C10a), 140.38 (C3), 140.86 (C1 ); MS: m/z (%) 333 (100) [M ],
335 (31) (M þ 2); Anal. Calcd. for: C20H16ClN3: C, 71.96; H, 4.83; N,
d: 24.28 (C5), 25.63 (C6), 26.31 (C7), 111.28 (C11), 116.24 (C7a), 118.51
12.59. Found: C, 71.92; H, 4.86; N, 12.54%.
(C8), 119.18 (C4a), 120.38 (C9), 121.63 (C10), 126.42 (C12b), 127.41 (C7b),
133.28 (C12a), 134.40 (C11a), 140.53 (C4), 159.11 (C2); MS: m/z (%) 251
(100) [Mþ], 252 (30) [M þ 2]; Anal. Calcd. for: C15H13N3O: C, 71.70; H,
5.21; N, 16.72. Found: C, 71.74; H, 5.26; N, 16.75%.
6.1.5. General procedure for the synthesis of 2-hydroxy-5,6,7,12-
tetrahydropyrimido [50,60:6,7]cyclohept[b]indoles (6)
A mixture of the appropriate 7-(hydroxymethylene)-7,8,9,10-
tetrahydrocyclohepta [b]indol-6(5H)-one (2, 0.001 mol) and urea
(0.002 mol) was refluxed in glacial acetic acid (6 ml) at 120 ꢁC for
5 h. After completion of the reaction it was then poured into crushed
ice with stirring. The solid thus separated was filtered, dried and
purified by column chromatography over silica-gel using a petro-
leum ether and ethyl acetate mixture (75:25) as the solvent system
to yield the corresponding 2-hydroxy-5,6,7,12-tetrahydropyrimido
[50,60:6,7]cyclohepta[b]indoles (6) as a yellow solid.
6.1.5.5. 9-Chloro-2-hydroxy-5,6,7,12-tetrahydropyrimido[50,60:6,7]
cyclohepta[b]indole (6e). Yellow solid; M.p. 197 ꢁC; Yield: 0.199 g
(70%); IR (KBr, cmꢀ1 nmax: 3430, 3268, 1602; 1H NMR (CDCl3,
)
500 MHz) (ppm) d: 2.08e2.14 (m, 2H, C6e2H), 2.90e2.93 (m, 2H,
C5e2H), 3.09e3.11 (m, 2H, C7e2H), 7.10 (d, 1H, C10eH, J ¼ 8.00 Hz),
7.18 (d,1H, C11eH, J ¼ 8.00 Hz), 7.29 (s,1H, C8eH), 7.49 (s,1H, C4eH),
9.25 (bs,1H, N12eH), 11.25 (s,1H, C2-OH); 13C NMR (CDCl3,125 MHz)
(ppm) d: 24.29 (C5), 25.43 (C6), 26.23 (C7), 112.12 (C11), 116.21 (C7a),
119.20 (C4a), 120.18 (C8), 123.42 (C10), 126.40 (C12b), 126.98 (C7b),
128.41 (C9), 133.24 (C12a), 133.98 (C11a), 140.38 (C4), 159.18 (C2); MS:
m/z (%) 285 (100) [Mþ]; Anal. Calcd. for: C15H12ClN3O: C, 63.05; H,
4.23; N, 14.71. Found: C, 63.09; H, 4.26; N, 14.75%.
6.1.5.1. 2-Hydroxy-9-methyl-5,6,7,12-tetrahydropyrimido[50,60:6,7]
cyclohepta[b]indole (6a). Yellow solid; M.p. 220 ꢁC; Yield: 0.185 g
(70%); IR (KBr, cmꢀ1 nmax: 3438, 3265, 1602; 1H NMR (CDCl3,
)
500 MHz) (ppm)
2.92e2.94 (m, 2H, C5e2H), 3.08e3.12 (m, 2H, C7e2H), 7.10 (d, 1H,
10eH, J ¼ 8.00 Hz), 7.21 (d, 1H, C11eH, J ¼ 8.00 Hz), 7.32 (s, 1H,
C8eH), 7.49 (s, 1H, C4eH), 9.19 (b s, 1H, N12eH), 11.30 (s,1H, C2-OH);
13C NMR (CDCl3, 125 MHz) (ppm)
: 21.48 (C9eCH3), 24.24 (C5),
d: 2.09e2.13 (m, 2H, C6e2H), 2.45 (s, 3H, C9eCH3),
6.1.6. General procedure for the synthesis of 2-mercapto-5,6,7,12-
tetrahydropyrimido [50,60:6,7]cyclohept[b]indoles (7)
A mixture of the appropriate 7-(hydroxymethylene)-7,8,9,10-
tetrahydrocyclohepta[b]indol-6(5H)-one (2, 0.001 mol) and thio-
urea (0.002 mol) was refluxed in glacial acetic acid (6 ml) at 120 ꢁC for
5 h. After completion of the reaction it was then poured into crushed
C
d
25.41 (C6), 26.38 (C7), 110.98 (C11), 116.41 (C7a), 119.17 (C4a), 120.11
(C8), 125.82 (C10), 126.68 (C12b), 127.38 (C7b), 129.31 (C9), 133.48