6368
M. Brændvang, L.-L. Gundersen / Bioorg. Med. Chem. 13 (2005) 6360–6373
chromatography; yield 115 mg (70%), yellow microcrys-
talline solid, mp 186–188 ꢁC. 1H NMR (CDCl3,
200 MHz) d 3.01 (s, 6H, CH3), 5.44 (s, 2H, CH2), 6.81
(d, J = 9.2 Hz, 2H, Ar), 7.31–7.32 (m, 5H, Ph), 7.99 (s,
1H, H-8), 8.77 (d, J = 9.2 Hz, 2H, Ar), 8.92 (s, 1H, H-
2); 13C NMR (CDCl3, 50 MHz) d 40.1 (CH3), 47.1
(CH2), 111.5 (CH in Ar), 123.1 (C in Ar), 127.7 (CH in
Ar), 128.3 (CH in Ar), 129.0 (CH in Ar), 129.8 (C-5),
131.2 (CH in Ar), 135.4 (C in Ar), 142.8 (C-8), 151.9
(C-4/C-6/C in Ar), 152.2 (C-4/C-6/C in Ar), 152.4 (C-
2), 155.0 (C-4/C-6/C in Ar); MS EI m/z (rel. %): 329
(100, M+), 328 (45), 312 (3), 238 (6), 184 (5), 165 (3),
164 (3), 91 (16); HRMS: Found 329.1651. Anal. Calcd
for C20H19N5: 329.1640. Found: C, 75.05; H, 5.98; N,
21.13. C20H19N5 requires C, 72.93; H, 5.81; N, 21.26.
5.13. 6-(2,4-Dimethylphenyl)-9-(phenylmethyl)-9H-purine
(2o)
The title compound was prepared by Negishi coupling
between
6-chloro-9-(phenylmethyl)-9H-purine
1a
(123 mg, 0.50 mmol) and 2,4-dimethylphenylzinc bro-
mide [generated in situ from 4-bromo-1,3-dimethyl-ben-
zene (84 lL, 0.60 mmol)] as described for compound 2c
and in Table 1. EtOAc–hexane (1:5) followed by
EtOAc–hexane (1:1) was used for flash chromatogra-
phy; yield 104 mg (66%), pale yellow crystalline com-
1
pound, mp 102–103 ꢁC. H NMR (CDCl3, 500 MHz)
d 2.37 (s, 3H, CH3), 2.43 (s, 3H, CH3), 5.45 (s, 2H,
CH2), 7.14–7.16 (m, 2H, Ar), 7.33–7.38 (m, 5H, Ph),
7.65 (d, J = 7.8 Hz, 1H, Ar), 8.04 (s, 1H, H-8), 9.06 (s,
1H, H-2); 13C NMR (CDCl3, 125 MHz) d 20.4 (CH3),
21.2 (CH3), 47.2 (CH2), 126.4 (CH in Ph), 127.8 (CH
in Ph), 128.5 (CH in Ph), 129.1 (CH in Ph), 130.8 (CH
in Ar), 131.9 (CH in Ar), 131.9 (C-5/C in Ar), 132.0
(C-5/C in Ar), 135.1 (C in Ph), 136.9 (C in Ar), 144.0
(C-8), 151.7 (C-4), 152.3 (C-2), 159.0 (C-6); MS EI m/z
(rel. %): 314 (29, M+), 224 (17), 223 (100), 208 (4), 195
(1), 194 (1), 169 (2), 91 (15); HRMS: Found 314.1528.
Anal. Calcd for C20H18N4: 314.1531. Found: C, 76.45;
H, 5.77; N, 17.70. C20H18N4 requires C, 76.41; H,
5.77; N, 17.82%.
5.11. 6-(4-Methylphenyl)-9-(phenylmethyl)-9H-purine
(2m)
The title compound was prepared by Suzuki coupling
between
6-chloro-9-(phenylmethyl)-9H-purine
1a
(123 mg, 0.50 mmol) and 4-methylphenylboronic acid
(0.75 mmol) as described for compound 2d and in Table
1. EtOAc–hexane (1:3) was used for flash chromatogra-
phy; yield 105 mg (70%), colorless small needles, mp
128–130 ꢁC. 1H NMR (CDCl3, 200 MHz) d 2.43 (s,
3H, CH3), 5.47 (s, 2H, CH2), 7.34–7.37 (m, 7H, Ar),
8.07 (s, 1H, H-8), 8.68 (d, J = 8.2 Hz, 2H, Ar), 9.01 (s,
1H, H-2); 13C NMR (CDCl3, 50 MHz) d 20.4 (CH3),
46.0 (CH2), 126.5 (CH in Ar), 127.2 (CH in Ar), 127.8
(CH in Ar), 128.1 (CH in Ar), 128.5 (CH in Ar), 129.5
(C-5), 131.7 (C in Ar), 134.0 (C in Ar), 140.1 (C in
Ar), 142.6 (C-8), 151.1 (C-4/C-6), 151.2 (C-2), 153.6
(C-4/C-6); MS EI m/z (rel. %): 300 (100, M+), 299
(100), 285 (3), 272 (6), 223 (6), 209 (17), 91 (46); HRMS:
Found 300.1364. Anal. Calcd for C19H16N4: 300.1375;
Found: C, 76.12; H, 5.29; N, 18.62. C19H16N4 requires
C, 75.98; H, 5.37; N, 18.65%.
5.14. 6-(4-tert-Butylphenyl)-9-(phenylmethyl)-9H-purine
(2p)
The title compound was prepared by Negishi coupling
between
6-chloro-9-(phenylmethyl)-9H-purine
1a
(123 mg, 0.50 mmol) and 4-tert-butylphenylzinc bro-
mide (0.60 mmol) as described for compound 2c and
in Table 1. EtOAc–hexane (1:4) was used for flash chro-
matography; yield 136 mg (80%), colorless microcrystal-
line solid, mp 143–145 ꢁC. 1H NMR (CDCl3, 200 MHz)
d 1.36 (s, 9H, t-Bu), 5.46 (s, 2H, CH2), 7.33 (m, 5H, Ph),
7.57 (d, J = 8.6 Hz, 2H, Ar), 8.06 (s, 1H, H-8), 8.67 (d,
J = 8.6 Hz, 2H, Ar), 9.02 (s, 1H, H-2); 13C NMR
(CDCl3, 50 MHz) d 31.2 (CH3 in t-Bu), 34.9 (C in t-
Bu), 47.2 (CH2), 125.6 (CH in Ar), 127.7 (CH in Ar),
128.4 (CH in Ar), 129.0 (CH in Ar), 129.5 (CH in Ar),
130.8 (C-5), 132.8 (C in Ar), 135.2 (C in Ar), 143.8 (C-
8), 152.3 (C-4/C-6), 152.5 (C-2), 154.3 (C in Ar), 155.0
(C-4/C-6); MS EI m/z (rel. %): 342 (44, M+), 328 (24),
237 (100), 299 (3), 163 (4), 91 (45); HRMS: Found
342.1837. Anal. Calcd for C22H22N4: 342.1844. Found:
C, 77.07; H, 6.60; N, 16.24. C19H16N4 requires C,
77.16; H, 6.47; N, 16.36%.
5.12. 6-(3,4-Dimethylphenyl)-9-(phenylmethyl)-9H-purine
(2n)
The title compound was prepared by Negishi coupling
between 6-chloro-9-(phenylmethyl)-9H-purine (196 mg,
0.80 mmol) and 3,4-dimethylphenylzinc bromide
(1.2 mmol) as described for compound 2c and in Table
1. EtOAc–hexane (1:2) was used for flash chromato-
graphy; yield 146 mg (58 %), colorless powdery crys-
tals, mp 156–158 ꢁC. 1H NMR (CDCl3, 500 MHz) d
2.33 (s, 3H, CH3), 2.37 (s, 3H, CH3), 5.44 (s, 2H,
CH2), 7.28–7.35 (m, 6H, Ph/Ar), 8.05 (s, 1H, H-8),
8.52 (s, 1H, Ar), 8.55 (d, J = 8.0 Hz, 1H, Ar), 9.00
(s, 1H, H-2); 13C NMR (CDCl3, 125 MHz) d 19.9
(2 · CH3), 47.2 (CH2), 127.6 (CH in Ar), 127.7 (CH
in Ar), 128.5 (CH in Ph), 129.1 (CH in Ph), 130.0
(CH in Ph), 130.4 (CH in Ar), 130.7 (C-5), 133.2 (C
in Ar), 135.2 (C in Ar), 136.9 (C in Ph), 140.2 (C in
Ar), 143.8 (C-8), 152.3 (C-4), 152.5 (C-2), 155.1 (C-
6); MS EI m/z (rel. %): 314 (100, M+), 313 (91), 299
(3), 223 (12), 91 (29); HRMS: Found 314.1525. Anal.
Calcd for C20H18N4: 314.1531; Found: C, 76.42; H,
5.70; N, 18.13. C20H18N4requires C, 76.41; H, 5.77;
N, 17.82%.
5.15. 6-(3-Chlorophenyl)-9-(phenylmethyl)-9H-purine (2q)
The title compound was prepared by Suzuki coupling be-
tween 6-chloro-9-(phenylmethyl)-9H-purine 1a (245 mg,
1.00 mmol) and 3-chlorophenylboronic acid (1.50 mmol)
as described for compound 2d and in Table 1. EtOAc–
hexane (1:3) was used for flash chromatography; yield
158 mg (49%), colorless small needles, mp 152–154 ꢁC.
1H NMR (CDCl3, 200 MHz) d 5.47 (s, 2H, CH2), 7.33–
7.34 (m, 5H, Ar), 7.45–7.49 (m, 2H, Ar), 8.09 (s, 1H, H-
8), 8.70–8.76 (m, 1H, Ar), 8.80 (br s, 1H, Ar), 9.04 (s,
1H, H-2); 13C NMR (CDCl3, 50 MHz) d 47.3 (CH2),