Pyridine → (3aR,4S,6R,6aS)-6-{4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxole-4-carbaldehyde

Participants

Reaction Steps

EDC.HCl (1.17 g, 6.11 mmol) was added to a solution of [(3aR,4R,6R,6aS)-6-{4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2,2-dimethylhexahydrocyclopenta[d][1,3]dioxol-4-yl]methanol (0.66 g, 2.04 mmol) in anhydrous DMSO (11 ml) and stirred at RT. Pyridine (0.33 ml, 4.08 mmol) followed by TFA (0.15 ml, 2.04 mmol) were added to the reaction mixture and stirred at RT (the reaction mixture becomes a slightly yellow solution). The reaction monitored by LCMS. The reaction mixture becomes dark brown after 30 mins. After 1.5 hrs, a further aliquot of EDC.HCl (583 mg, 3.06 mmol) was added and allowed to stir for a further 1.5 hrs at RT. The reaction mixture was diluted with EtOAc (50 ml). This was washed with brine (2×50 ml), dried over Na2SO4 and evaporated in vacuo. The crude product was absorbed onto silica gel (3 ml) placed onto a silica column and purified eluting with EtOAc/heptanes (4/6) to yield a colorless oil (260 mg 40%); MS (ESI+) for C15H16ClN3O3 m/z 1 [M+H]+, 321.90; HPLC purity>95% (ret. time, 1.72 min). 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 1.28-1.46 (3H, m), 1.54-1.77 (3H, m), 2.27-2.97 (2H, m), 3.17 (1H, td, J=8.72, 4.34 Hz), 4.82-5.13 (2H, m), 5.13-5.39 (1H, m), 6.45-6.84 (1H, m), 7.03-7.26 (1H, m), 8.47-8.86 (1H, m), 9.86 (1H, s).

Provenance & Evidence