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M. Hocek et al. / Tetrahedron 59 (2003) 607–611
CH(CH3)2); 6.84 (d, 2H, J¼8.2 Hz, H-arom.); 7.05 (d, 2H,
J¼8.4 Hz, H-arom.); 7.42 (d, 2H, J¼8.2 Hz, H-arom.); 8.07
(s, 1H, H-8); 8.78 (d, 2H, J¼8.4 Hz, H-arom.). 13C NMR
(100.6 MHz, CDCl3): 22.57 (CH(CH3)2); 45.15 (CH2);
46.79 (CH(CH3)2); 55.21 and 55.33 (2£OCH3); 113.67,
113.91, 130.15 and 131.43 (CH-arom.); 128.93, 128.99 and
131.68 (2£C-i-arom. and C-5); 140.96 (CH-8); 152.64,
154.06 and 158.09 (C-2, C-4 and C-6); 161.72 and 163.39
(2£C-OMe). Exact mass (EI HR MS) found: 388.1907; for
C23H24N4O2 calculated: 388.1899.
131.50 (2£C-i-arom. and C-5); 141.19 (CH-8); 151.49,
158.11 and 158.23 (C-2, C-4 and C-6); 160.50 and 163.71
(2£C-OMe). Exact mass (EI HR MS) found: 402.2064; for
C24H26N4O2 calculated: 402.2056. Anal. calcd for
C24H26N4O2 (402.5): C, 71.62; H, 6.51; N, 13.92; found:
C, 71.24; H, 6.58; N, 13.63.
3.2.7. 9-Isopropyl-2,6-bis[(4-methoxyphenyl)ethynyl]-
purine (8). DMF (5 ml) and Et3N (2 ml) were added
through septum to an argon purged flask containing 2,6-
dichloropurine 1 (690 mg, 3 mmol), (4-methoxyphenyl)-
acetylene14 (1.32 g, 10 mmol), CuI (200 mg, 1 mmol) and
Pd(PPh3)4 (200 mg, 0.174 mmol). The mixture was then
stirred at 1208C for 12 h and left overnight at ambient
temperature. The solvents were evaporated in vacuo and the
residue was chromatographed on a silica gel column (150 g,
ethyl acetate–light petroleum 1:2) to give compound 8 as
yellow amorphous solid (500 mg, 39%). FAB MS, m/z: 423
(20) [M], 279 (18), 135 (100). IR (CHCl3), n¼2211, 1605,
1569, 1512, 1487, 1465, 1379, 1295, 1252 cm21. 1H NMR
(500 MHz, CDCl3): 1.66 (d, 6H, J¼6.8 Hz, CH(CH3)2);
3.84 and 3.85 (2£s, 2£3H, 2£OCH3); 5.03 (sept., 1H,
J¼6.8 Hz, CH(CH3)2); 6.90 (d, 2H, J¼8.4 Hz, H-arom.);
6.92 (d, 2H, J¼8.2 Hz, H-arom.); 7.65 (d, 2H, J¼8.7 Hz,
H-arom.); 7.71 (d, 2H, J¼8.7 Hz, H-arom.); 8.24 (s, 1H,
H-8). 13C NMR (100.6 MHz, CDCl3): 22.70 (CH(CH3)2);
47.21 (CH(CH3)2); 55.28 and 55.32 (2£OCH3); 83.38,
87.01, 87.65 and 99.38 (Cu); 113.45 and 113.74 (2£C-i-
arom.); 114.03, 114.12, 134.16 and 134.51 (CH-arom.);
133.01 (C-5); 143.23 (CH-8); 142.43, 146.74 and 151.32
(C-2, C-4 and C-6); 160.48 and 160.99 (2£C-OMe). Exact
mass (FAB HR MS) found: 423.1819; for C26H23N4O2
[MþH] calculated: 423.1821.
3.2.4. 9-Isopropyl-6-(4-methoxybenzyl)-2-(4-methoxy-
phenyl)purine (5). Prepared from 3 by procedure A
(1.5 equiv. of boronic acid) in 95%. Colorless oil. EI MS,
m/z: 388 (100) [M], 345 (45), 277 (15), 149 (40). IR (KBr),
n¼1610, 1593, 1511, 1494, 1465, 1438, 1389, 1375, 1302,
1250 cm21 1H NMR (400 MHz, CDCl3): 1.66 (d, 6H,
.
J¼6.8 Hz, CH(CH3)2); 3.75 and 3.88 (2£s, 2£3H,
2£OCH3); 4.47 (s, 2H, CH2); 4.95 (sept., 1H, J¼6.8 Hz,
CH(CH3)2); 6.83 (d, 2H, J¼8.6 Hz, H-arom.); 7.00 (d, 2H,
J¼8.8 Hz, H-arom.); 7.48 (d, 2H, J¼8.6 Hz, H-arom.); 8.03
(s, 1H, H-8); 8.50 (d, 2H, J¼8.8 Hz, H-arom.). 13C NMR
(100.6 MHz, CDCl3): 22.56 (CH(CH3)2); 38.76 (CH2); 47.12
(CH(CH3)2); 55.17 and 55.34 (2£OCH3); 113.68, 113.79,
129.79 and 130.36 (CH-arom.); 130.41, 130.86 and 131.26
(2£C-i-arom. and C-5); 141.46 (CH-8); 151.69 (C-4); 158.19,
158.44, 160.29 and 161.19 (C-2, C-6, 2£C-OMe). Exact mass
(EI HR MS) found: 388.1911; for C23H24N4O2 calculated:
388.1899.
3.2.5. 9-Isopropyl-2,6-bis(4-methoxyphenyl)purine (6).
Prepared from 1 by procedure A (3 equiv. of boronic acid)
in94%. Colorless crystals, mp175–1768C (CH2Cl2/ heptane).
EI MS, m/z: 374 (80) [M], 332 (59), 149 (100). IR (KBr),
n¼1609, 1588, 1565, 1513, 1433, 1372, 1246 cm21. 1H NMR
(400 MHz, CDCl3): 1.64 (d, 6H, J¼6.6 Hz, CH(CH3)2); 3.84
and 3.85 (2£s, 2£3H, 2£OCH3); 4.97 (sept., 1H, J¼6.6 Hz,
CH(CH3)2); 6.98 (d, 2H, J¼8.5 Hz, H-arom.); 7.04 (d, 2H,
J¼8.5 Hz, H-arom.); 8.03(s, 1H, H-8); 8.56(d, 2H, J¼8.5 Hz,
H-arom.); 8.88 (d, 2H, J¼8.5 Hz, H-arom.). 13C NMR
3.2.8. 9-Isopropyl-2,6-bis[2-(4-methoxyphenyl)ethyl]-
A solution of compound 8 (395 mg,
purine (9).
0.94 mmol) in dioxane (120 ml and EtOH (50 ml) was
hydrogenated under atmospheric pressure in the presence of
5% Pd/C (200 mg) for 24 h at ambient temperature. The
catalyst was filtered off on Celite and the solvents were
evaporated. Column chromatography of the complex
mixture gave compound 9 as yellow oil (55 mg, 14%). EI
MS, m/z: 430 (37) [M], 387 (11), 277 (15), 149 (20), 121
(100). IR (CHCl3), n¼1610, 1592, 1513, 1497, 1392,
(100.6 MHz,
CDCl3):
22.59
(CH(CH3)2);
47.00
(CH(CH3)2); 55.34 (2£OCH3); 113.69, 113.90, 129.77 and
131.43(CH-arom.); 129.19and 129.31 (2£C-i-arom.); 131.50
(C-5); 141.28 (CH-8); 152.96, 153.72 and 158.02 (C-2, C-4
and C-6); 161.24 and 161.75 (2£C-OMe). Exact mass (EI HR
MS) found: 374.1754; for C22H22N4O2 calculated: 374.1743.
Anal. calcd for C22H22N4O2 (374.4): C, 70.57; H, 5.92; N,
14.96; found: C, 70.56; H, 5.92; N, 14.95.
1246 cm21 1H NMR (500 MHz, CDCl3): 1.61 (d, 6H,
.
J¼6.8 Hz, CH(CH3)2); 3.13–3.16 (m, 4H, 2£CH2); 3.30–
3.34 (m, 2H, CH2); 3.43–3.46 (m, 2H, CH2); 3.77 (s, 6H,
2£OCH3); 4.90 (sept., 1H, J¼6.8 Hz, CH(CH3)2); 6.80 (d,
2H, J¼8.6 Hz, H-arom.); 6.81 (d, 2H, J¼8.5 Hz, H-arom.);
7.17 (d, 2H, J¼8.5 Hz, H-arom.); 7.22 (d, 2H, J¼8.5 Hz,
H-arom.); 8.02 (s, 1H, H-8). 13C NMR (100.6 MHz,
CDCl3): 22.54 (CH(CH3)2); 33.50, 34.11, 35.17 and 41.08
(CH2); 46.90 (CH(CH3)2); 55.12 and 55.21 (2£OCH3);
113.66, 113.72, 129.40 and 129.43 (CH-arom.); 133.62,
133.95 and 136.82 (2£C-i-arom. and C-5); 140.86 (CH-8);
151.00, 157.79, 157.86, 161.17 and 164.08 (C-2, C-4 and
C-6 and 2£C-OMe). Exact mass (EI HR MS) found:
430.2358; for C26H30N4O2 calculated: 430.2369.
3.2.6. 9-Isopropyl-2,6-bis(4-methoxybenzyl)purine (7).
Prepared from 1 by procedure B (3 equiv. of organozinc
reagent) in 90%. Colorless oil. EI MS, m/z: 402 (100) [M],
359 (34), 345 (11), 149 (21). IR (KBr), n¼1611, 1594, 1513,
1496, 1464, 1442, 1391, 1382, 1325, 1301, 1249 cm21. 1H
NMR (400 MHz, CDCl3): 1.58 (d, 6H, J¼6.7 Hz,
CH(CH3)2); 3.74 and 3.77 (2£s, 2£3H, 2£OCH3); 4.27
and 4.40 (2£s, 2£2H, 2£CH2); 4.85 (sept., 1H, J¼6.7 Hz,
CH(CH3)2); 6.79 (d, 2H, J¼9.0 Hz, H-arom.); 6.81 (d, 2H,
J¼8.9 Hz, H-arom.); 7.32 (d, 2H, J¼8.3 Hz, H-arom.); 7.39
(d, 2H, J¼8.3 Hz, H-arom.); 8.00 (s, 1H, H-8). 13C NMR
(100.6 MHz, CDCl3): 22.51 (CH(CH3)2); 38.65 and 44.93
(2£CH2); 46.95 (CH(CH3)2); 55.17 and 55.22 (2£OCH3);
113.63, 113.78, 130.11 and 130.32 (CH-arom.); 130.73,
Acknowledgements
This work is a part of research project Z4 055 905. It was