Bromotrimethylsilane → [(E)-4-(2,6-diaminopurin-9-yl)but-1-enyl]phosphonic acid

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Reaction Steps

To a solution of (E)-2,6-diamino-9-[4-(diisopropoxy-phosphoryl)but-3-enyl]purine (144mg, 391 μmol) in dichloromethane (10 ml) was added bromotrimethylsilane (1.20 g, 7.82 mmol) and the mixture stirred at room temperature under dry nitrogen for 18 hr. The resulting white suspension was evaporated to dryness and the residue azeotroped with methanol (×6). The residue was purified by column chromatography on reverse phase silica gel eluting with water to give a product which n.m.r. analysis showed to be the monoester. To a suspension of the monoester (approx. 306 μmol) in dry N,N-dimethylformamide (10 ml) was added bromotrimethylsilane (1.16 g, 7.58 mmol) and the resulting solution was stirred at room temperature under dry nitrogen for 18 hr. The solution was evaporated to dryness and the residue azeotroped with methanol (×3) then acetone-water (1:1) (×3). The residue was purified by column chromatography on reverse phase silica gel eluting with water to give (E)-2,6-diamino-9-(4-phosphonobut-3 -enyl)purine as a white solid (30 mg, 27%), m.p. >325° C.; λmax (MeOH) 256 (6,570) and 285 (6,490)nm; υmax (KBr) 3410, 1710, 1670, 1630, 1590, 1420, 1220 and 135 cm-1 ; δH [(CD3)2SO+one drop NH4OH solution] 2.50 (2H, m, CH2) 4.05 (2H, t, J 7 Hz, CH2N), 5.70 (1H, pseudo-t, J 17 Hz, PCH=CH), 5.81 (2H, s, NH2), 6.10 (1H, pseudo-tt, J 7 Hz and 20 Hz, PCH=CH), 6.69 (2H, s, NH2) , 7.76 (1H, s, H-8); FABMS thioglycerol) 285 (MH+).

Provenance & Evidence