Pyrimidine → 4-amino-5-(4-phenoxyphenyl)-7-(3-tetrahydrofuryl)-7H-pyrrolo[2,3-d]pyrimidine

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Reaction Steps

To a stirred suspension of 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (4.83 g, 16 mmol) in N,N-dimethylformamide (80 mL), under an d]pyrimidine (4.83 g, 16 mmol) in N,N-dimethylformamide (80 mL), under an atmosphere of nitrogen, was added 60% sodium hydride in mineral oil (0.75 g, 19 mmol), and the mixture stirred at room temperature for 30 minutes. The resultant dark solution was treated with a solution of 4-{(S)-tetrahydrofuran-3-yl}toluenesulphonate (4.20 g, 18 mmol) in N,N-dimethylformamide (20 mL) in 2 mL aliquots. The resultant solution was stirred at room temperature for 30 minutes, then at 95 deg. C. for 18 hours. The solution was allowed to cool to ambient temperature, then poured onto ice/water (200 mL). The aqueous was extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with water (4×150 mL), dried over sodium sulphate, and the solvent was removed under reduced pressure. The residue was warmed with dichloromethane (1000 mL) until a solution was obtained, cooled to ambient temperature, and purified by chromatography with a Biotage 40M column using ethyl acetate/triethylamine (95:5), then ethyl acetate/triethylamine/methanol (90:5:5) as a mobile phase, to yield R-(+)-4-[4-amino-5-(4-phenoxyphenyl)-7-(3-tetrahydrofuryl)-7H-pyrrolo[2,3-d]pyrimidine as an off-white solid (4.35 g, 12 mmol) melting point 165-166 deg. C., LC/MS: Hypersil BDS c18 (100×2.1 mm) 0.1M ammoniumacetate/acetonitrile, 10-100% acetonitrile in 8 min.) MH+373 tr=4.44 minutes. [ ]D+20.5±0.6 (dichloromethane, 22.6 deg. C.)

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