| 69.5% |
With triphenylphosphine; bis(dibenzylideneacetone)-palladium(0); In N,N-dimethyl-formamide; at 20℃; under 760.051 Torr; for 48h;Inert atmosphere; |
General procedure: An argon-filled 1L round bottomflask was charged with: 5-iodo-2-deoxycytidine (30 g, 85 mmol); benzylamine (109.3 g, 1020 mmol, 12 eq); and anhydrous N,N-dimethylformamide (DMF, 205 mL). The mixture was rapidly magnetically stirred until all the solids had dissolved. The resulting solution was degassed by two cycles of evacuation to 50 mm and refilling with argon. A mixture of bis(dibenzylidineacetone)palladium(0) (978 mg, 1.7 mmol, 0.02 eq) and triphenylphosphine (1.92 g, 7.3 mmol, 0.086 eq) was added and the resulting fine black suspension was rapidly stirred, evacuated to 50 mm and filled with carbon monoxide (1 atm) from a rubber balloon. The mixture was stirred at room temperature (?20 C) and periodically refilled with carbon monoxide. After 26 hours, the reaction was found to be complete by TLC analysis (silica gel, eluent: 15% methanol/85% dichloromethane (v/v), Rf(SM) = 0.3, Rf(5a) = 0.4). The reaction mixture was diluted with ethyl acetate (205 mL), filtered, and rinsed forward with 65% ethyl acetate/35%DMF (100 mL). The clear green filtrate was concentrated on a rotary evaporator (50-80 C, 1-2 mm) until all the solvents and most of the benzylamine had distilled. The dark orange residue (?75 g) was dissolved in hot abs. ethanol (650 mL) and rapidly hot-filtered to remove a small amount of insoluble flakes (?2 g). The clear filtrate was allowed to cool with slow stirring and the product crystallized as needles. After stirring overnight, the slurry was filtered and the cake washed with ice-cold ethanol (100 mL). After drying in vacuo, the product 5a was obtained as a white, crystalline solid: 22.0 g,72% yield, mp 193-4 C. |
| 69.5% |
With triphenylphosphine; bis(dibenzylideneacetone)-palladium(0); In N,N-dimethyl-formamide; at 20℃; under 760.051 Torr; for 48h; |
Prepared as described for (4a) (40 nmol scale), using 3-phenylpropylamine (6 eq) in place of benzylamine and a reaction time of 48 hours at room temperature. After removal of the solvents on the rotovap, the residue was triturated with diethyl ether (-30 mL/g) to extract the excess 3- phenylpropylamine and the gummy residue was dissolved in hot ethanol, stirred at room temperature for 18 h, followed by stirring at 0C for 1 h. The resulting mixture was filtered and the mother liquor was evaporated resulting in a brown resin. This was dissolved in warm mixture of dichloromethane and water. After standing and stirring at room temperature, white feathery crystals formed in the organic layer, and in the aqueous layer as well. The triphasic mixture was filtered and the filter cake was washed with diethyl ether to afford (4c) as a fluffy white solid (10.78 g, 69.5% yield). 1H NMR (500 MHz, d6-DMSO): delta = 8.39 (s, 1H), 8.13 (t, J = 5.3 Hz, 1H), 8.05 (bs, 1H), 7.71 (bs, 1H), 7.28 (t, J= 7.4, 2H), 7.22 (d, J= 7.0, 2H), 7.17 (t, J= 7.4, 1H), 6.13 (t, J= 6.4 Hz, 1H), 5.22 (d, J= 4.3 Hz, 1H), 5.07 (t, J= 5.5 Hz, 1H), 4.26 (dt, J= 9.4, 4.1 Hz, 1H), 3.83 (dd, J= 7.8, 3.9 Hz, 1H), 3.66 (m, 1H), 3.58 (m, 1H), 3.19 (dd, J= 12.9, 6.7 Hz, 2H), 2.61 (t, J= 7.5 Hz, 2H), 2.19 (m, 2H), 1.78 (m, J= 7.4 Hz, 2H). 13C NMR (500 MHz, d6-DMSO): delta = 165.34 (1C), 163.56 (1C), 153.60 (1C), 143.53 (1C), 141.70 (1C), 128.38 (2C), 128.33 (2C), 125.78 (1C), 98.99 (1C), 87.63 (1C), 85.86 (1C), 69.82 (1C), 60.96 (1C), 40.36 (1C), 38.58 (1C), 32.63 (1C), 32.63 (1C). MS m/z: [Mu-] calcd for C19H23N405, 387.42; found, 387.1 (ESI). |
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