Sodium hydride → tert-butyl4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-piperidinecarboxylate

Participants

Reaction Steps

To a solution of 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (2.0 g, 6.6 mmol) in dry DMF (100 ml) under nitrogen at 0° C. was added NaH (0.264 g, 60% dispersion, 6.6 mmol) and the reaction mixture warmed to room temperature and stirred for 1 hr. Tert-butyl 4-[(4-methylphenyl)sulfonyl]oxy-1-piperidinecarboxylate (2.34 g, 6.6 mmol) was added and the resulting solution heated at 95° C. for 72 hr. The reaction was quenched by careful addition of water (150 ml). Extract with EtOAc (3×100 ml) and wash with water (4×100 ml) and brine (2×100 ml). The organic solution was dried (Na2SO4), filtered and evaporated to leave a solid which was adsorbed onto silica and purified by flash silica gel column chromatography using EtOAc then 5% MeOH/EtOAc as eluent to give in F 13-22 tert-butyl4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-piperidinecarboxylate (1.0 g, 31%) as a white solid, m.pt. 168.5-169.5° C. Rf in 10% EtOAc/MeOH=0.4. 1H NMR (d6 DMSO, 250 MHz): δ 8.14 (1H, s), 7.38-7.49 (5H, m), 7.07-7.23 (5H, m), 6.14 (2H, bs), 4.76 (1H, m), 4.11 (2H, m), 2.93 (2H, m), 1.92-2.02 (4H, m), 1.43 (9H, s). Mass spec. C28H31O3N5 (485.2430). IR (KBr disc): 3059, 1695, 1588, 1235 cm−1.

Provenance & Evidence