S. Naya et al. / Tetrahedron 60 (2004) 459–467
465
1
3
H-3), 9.87 (1H, br s, NH), 9.91 (1H, s, OH); C NMR
150.9 MHz, DMSO-d ) d 13.8, 19.7, 30.3, 39.6, 47.2, 89.3,
H-6), 8.19 (1H, d, J¼9.8 Hz, H-3), 10.05 (1H, br s, NH),
1
3
(
10.14 (1H, s, OH); C NMR (150.9 MHz, DMSO-d ) d
6
6
1
1
3
23.0, 126.9, 127.3, 128.4, 133.5, 135.4, 137.9, 142.0,
43.0, 145.5, 151.7, 161.4, 161.9, 166.0; IR (KBr) n 3410,
47.2, 89.2, 123.1, 126.7, 127.0, 127.3, 127.9, 128.5, 129.6,
133.6, 135.4, 137.3, 137.9, 142.1, 143.1, 145.2, 151.5,
161.8, 161.9, 166.1; IR (KBr) n 3410, 3286, 1685,
21
þ
255, 1670, 1589, 1576 cm ; MS (FAB) m/z 378 (M þH);
1581 cm2 ; MS (FAB) m/z 398 (M þH); HRMS calcd
1
þ
HRMS calcd for C H N O : 378.1881 (MþH). Found:
2
2 23 3 3
þ
3
78.1849 (M þH).
for C H N O : 398.1504 (MþH). Found: 398.1530
2
4 19 3 3
þ
(
M þH).
4
.3. Reaction of 6a,f with TFA
4.5.2. 6-Benzyl-9-phenylcyclohepta[b]pyrimido[5,4-d]
pyrrole-8(6H),10(9H)-dione (7g). Yellow powder; mp
299–301 8C (from EtOH). H NMR (500 MHz, CDCl ) d
3
A solution of 6a,f (0.5 mmol) in CHCl (5 mL) and TFA
3
1
(0.5 mL) was stirred at rt for 0.5 h. To the mixture was
added EtOH (50 mL) and the precipitates were collected by
filtration to give 4a,f (4a: 95%, 4b: 100%).
5.73 (2H, s, CH ), 7.27–7.38 (7H, m, o-Ph, Bn), 7.41 (1H, t,
2
J¼7.4 Hz, p-Ph), 7.51 (2H, dd, J¼8.3, 7.4 Hz, m-Ph), 7.67
(
1H, dd, J¼9.3, 9.3 Hz, H-3), 7.74 (1H, dd, J¼9.7, 9.3 Hz,
4
.4. Thermal cyclization of 6a,f
H-4), 7.83 (1H, d, J¼9.7 Hz, H-5), 7.88 (1H, dd, J¼10.6,
1
3
9
.3 Hz, H-2), 9.24 (1H, d, J¼10.6 Hz, H-1); C NMR
A solution of 6a,f (0.05 mmol) in 1,4-dioxane (5 mL) was
stirred at 90 8C for 5 h. The mixture was cooled to rt, and the
resulting precipitates were collected by filtration to give
(125.7 MHz, CDCl ) d 45.4, 99.5, 123.0, 127.2, 128.1,
3
128.4, 128.8, 129.2, 129.3, 132.6, 134.6, 136.0, 136.4,
136.8, 138.8, 144.1, 148.5, 159.3, 161.6, 164.8; IR (KBr) n
1
þ
7
was identical with the authentic specimen.
a,f. The results are summarized in Table 1. Compound 7a
1
1684, 1654, 1586, 1508 cm2 ; MS (FAB) m/z 380 (M þH);
3
HRMS calcd for C H N O : 380.1399 (MþH). Found:
2
4 17 3 2
þ
3
80.1379 (M þH). Anal. calcd for C H N O ·1/2 H O:
2
4
17
3
2
2
4.4.1. 6-Benzyl-9-buthylcyclohepta[b]pyrimido[5,4-d]
pyrrole-8(6H),10(9H)-dione (7f). Orange plates; mp
C, 74.21; H, 4.67; N, 10.82. Found: C, 74.3; H, 4.4; N,
10.7%.
1
2
03–205 8C (from EtOH). H NMR (400 MHz, CDCl ) d
3
0
.98 (3H, t, J¼7.3 Hz, Bu-4), 1.45 (2H, sex, J¼7.3 Hz,
4.5.3. N-(1-Benzyl-1,2-dihydro-2-oxocyclohepta[b]pyr-
rol-3-yl)carbonyl-N -phenylurea (8). Yellow needles; mp
0
232–233 8C (from AcOEt). H NMR (500 MHz, CDCl ) d
Bu-3), 1.73 (2H, quint, J¼7.3 Hz, Bu-2), 4.13 (2H, t,
1
J¼7.3 Hz, Bu-1), 5.68 (2H, s, CH ), 7.23–7.36 (5H, m, Bn),
2
3
7
9
.65 (1H, dd, J¼9.3, 9.3 Hz, H-3), 7.71 (1H, dd, J¼9.3,
.3 Hz, H-4), 7.76 (1H, d, J¼9.3 Hz, H-5), 7.88 (1H, dd,
5.30 (2H, s, CH ), 7.09 (1H, t, J¼7.5 Hz, p-Ph), 7.21–7.36
2
(7H, m, m-Ph, Bn), 7.43 (1H, dd, J¼10.0, 9.0 Hz, H-6), 7.46
(1H, d, J¼9.5 Hz, H-8), 7.54 (1H, dd, J¼10.0, 9.5 Hz, H-7),
7.63 (2H, d, J¼7.5 Hz, o-Ph), 7.72 (1H, dd, J¼11.0, 9.0 Hz,
H-5), 9.45 (1H, d, J¼11.0 Hz, H-4), 10.89 (1H, s, NH),
1
3
J¼10.5, 9.3 Hz, H-2), 9.29 (1H, d, J¼10.5 Hz, H-1); C
NMR (125.7 MHz, CDCl ) d 13.9, 20.4, 30.3, 40.6, 45.2,
9
1
1
3
9.2, 122.7, 127.1, 128.2, 129.0, 132.3, 134.6, 135.7, 136.0,
38.4, 143.6, 148.2, 159.3, 161.4, 164.0; IR (KBr) n 1683,
1
3
10.91 (1H, s, NH); C NMR (125.7 MHz, CDCl ) d 43.9,
3
2
1
þ
635, 1588, 1508 cm ; MS (FAB) m/z 360 (M þH);
99.1, 118.8, 120.1, 123.7, 127.0, 128.1, 128.9, 129.1, 131.7,
133.5, 135.2, 137.6, 138.1, 145.5, 148.1, 151.3, 165.0,
167.1; IR (CHCl ) n 1675, 1653, 1589, 1539, 1478,
HRMS calcd for C H N O : 360.1712 (MþH). Found:
2
2 21 3 2
þ
2.79; H, 5.94; N, 11.57. Found: C, 73.0; H, 5.9; N, 11.7%.
3
7
60.1669 (M þH). Anal. calcd for C H N O ·1/5H O: C,
2
2
21
3
2
2
3
1447 cm2 ; MS (FAB) m/z 398 (M þH); HRMS calcd
1
þ
for C H N O : 398.1505 (MþH). Found: 398.1469
2
4 19 3 3
þ
N, 10.57. Found: C, 72.3; H, 4.9; N, 10.3%.
4
.5. Reaction of 4g with benzylamine
(M þH). Anal. calcd for C H N O : C, 72.53; H, 4.82;
2
4 19 3 3
A solution of 4g (145 mg, 0.5 mmol) and benzylamine
(
107 mg, 1.0 mmol) in CH Cl (5 mL) was stirred at rt for
2
4.6. Ring transformation of 4a to 7a–e
2
0
.5 h. To the mixture was added EtOH (50 mL) and the
precipitates were collected by filtration to give 6g (109 mg,
5%). The filtrate was concentrated in vacuo and the
resulting residue was purified by column chromatography
To a solution of 4a (46.5 mg, 0.2 mmol) in 1,4-dioxane
(20 mL) was added amine (0.4 mmol). The mixture was
stirred at 90 8C until the reaction was completed (Table 2).
The mixture was cooled to rt and the resulting precipitates
were collected by filtration to give 7a–e. The results are
summarized in Table 2. Compounds 7a–d were identical
5
on SiO using AcOEt as the eluent to give 8 (48 mg, 24%).
2
On the other hand, a solution of 4g (145 mg, 0.5 mmol) and
benzylamine (107 mg, 1.0 mmol) in CH Cl (5 mL) was
1
3
with the authentic specimen.
2
2
stirred at rt for 24 h. The mixture was concentrated in vacuo
and the resulting residue was chromatographed on SiO2
using AcOEt as the eluent to give 7g (32 mg, 17%) and 8
4.6.1. 6-Dimehtylaminophenyl-9-methylcyclohepta[b]-
pyrimido[5,4-d]pyrrole-8(6H),10(9H)-dione (7e). Red-
1
(
139 mg, 70%).
dish powder; mp.310 8C (from MeOH/CH Cl ).
H
NMR (400 MHz, CDCl ) d 3.05 (6H, s, NMe ), 3.49 (3H,
2
2
3
2
0
hydroxy-1-phenylpyrimidine-2(3H),6(1H)-dione
0
0
0
4
.5.1. 5-(1 -Benzyliminocycloheptatrien-2 -yl)-4-
(6g).
s, NMe), 6.85 (2H, d, J¼9.0 Hz, H-3 , H-5 ), 7.24 (2H, d,
13
0 0
J¼9.0 Hz, H-2 , H-6 ), 7.65–7.80 (3H, m, H-2, H-4, H-5),
1
Orange powder; mp 167–169 8C dec (from CH Cl ). H
2
7.86–7.93 (1H, m, H-3), 9.33 (1H, d, J¼10.5 Hz, H-1);
C
NMR (125.7 MHz, CDCl ) d 27.5, 40.5, 99.0, 113.0, 120.8,
2
NMR (500 MHz, DMSO-d ) d 4.71 (2H, s, CH ), 7.20 (1H,
2
6
3
d, J¼8.2 Hz, H-7), 7.26–7.41 (9H, m, Ph, H-5, o-Bn, p-Bn),
123.5, 128.8, 132.3, 135.7, 136.1, 138.2, 142.9, 150.5,
151.2, 159.7, 161.9, 165.2; IR (KBr) n 1682, 1635, 1592,
7
.33–7.37 (2H, m, m-Bn), 7.70 (1H, dd, J¼10.0, 8.2 Hz,