Job/Unit: O20168
/KAP1
Date: 10-04-12 15:00:25
Pages: 6
F. Chevot, R. Vabre, S. Piguel, M. Legraverend
SHORT COMMUNICATION
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that can easily be introduced and carried through a syn-
thetic sequence, remaining inert under numerous reaction
conditions. Under specific conditions, however, they can be
activated leading to Suzuki,[42] Sonogashira,[44] or
Stille[42,45,46] type reactions. Thus, we have shown that the
phenylsulfanyl group at the 6-position of a purine can be
involved in a cross-coupling reaction leading to the forma-
tion of a carbon–carbon bond. Providing that the THP pro-
tecting function at the 9-position can be removed as already
shown previously,[24] the method reported in this communi-
cation furnishes a new practical route to 6,8,9-trisubstituted
purines that have not been reported before. Furthermore, it
opens a route to the solid-phase combinatorial synthesis of
6,8,9-trisubstituted purine libraries through the binding of
intermediate 3 to a sulfur-linked Merrifield resin as a trace-
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Experimental Section
General Procedure for the Synthesis of 8-Amido- and 8-Amino-
purines: A 20-mL flame-dried reaction tube was charged under an
atmosphere of argon with 8-iodo-6-phenylthio-9-(tetrahydro-2H-
pyran-2-yl)-9H-purine (3, 0.23 mmol), tris(dibenzylideneacetone)
dipalladium (2 mol-%), 4,5-bis(diphenylphosphanyl)-9,9-dimeth-
ylxanthene (Xantphos, 6 mol-%), cesium carbonate (1.5 equiv.),
and the appropriate amide or amine (1.2 equiv.) in dry dioxane
(2 mL). The sealed tube was warmed at 120 °C for 4 h. After cool-
ing to room temperature, the reaction mixture was diluted with
EtOAc and washed with brine. The organic phase was dried with
MgSO4, filtered, and concentrated under vacuum. The resulting
crude product was purified by flash chromatography on silica gel
(gradient cyclohexane/AcOEt) to afford the desired product.
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N-[6-(Phenylthio)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-8-yl]benz-
amide (5a): Product 5a was obtained as a white solid (90 mg, 92%).
1H NMR (300 MHz, CDCl3): δ = 11.87 (br., 1 H), 8.65 (s, 1 H),
8.25 (s, 2 H), 7.74–7.64 (m, 2 H), 7.61–7.40 (m, 7 H), 6.03 (d, J =
10.2 Hz, 1 H), 4.27 (d, J = 10.4 Hz, 1 H), 3.81 (t, J = 11.7 Hz, 1
H), 2.14 (d, J = 11.0 Hz, 1 H), 1.99–1.60 (m, 5 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 177.1, 152.9, 152.1, 149.6, 147.8, 136.7,
135.1, 132.1, 130.3, 129.9, 129.3, 128.2, 127.0, 118.8, 82.3, 69.5,
28.2, 24.9, 23.3 ppm. MS (ESI+): m/z (%) = 454 (80) [M + Na]+,
432 (30) [M + H]+, 348 (100) [M – THP]+. HRMS (ESI): calcd.
for C23H21N5O2SNa [M + Na] 454.1314; found 454.1303.
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental details; characterization data; and copies of the
1H NMR, 13C NMR, and mass spectra of all compounds.
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Acknowledgments
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Marianne Bombled is acknowledged for providing MS data. We
thank the Ministère de l’Enseignement Supérieur et de la Recher-
che for doctoral fellowships of F. C. and R. V.
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