1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]heptanenitrile

Participants

Reaction Steps

To a solution of 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (6.1 g, 19 mmol) in acetonitrile (58 mL) was added crude hept-2-enenitrile (2.6 g, 23 mmol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (3.49 mL, 23.4 mmol). The resulting mixture was stirred at room temperature over the weekend and then evaporated to dryness. The residue was purified on silica gel, eluting with 0 to 50% of ethyl acetate in hexane, to give the desired product (6.90 g, 84%). LCMS calculated for C22H33N6OSi(M+H)+: m/z=425.2. Found: 425.4. The racemic mixture was applied on an OD-H column (3×25 cm, 5 μM), eluting with 15% ethanol and 85% hexane mixture at a flow rate of 28 mL/min to give the two desired enantiomers. First peak retention time of 9.46 min; second peak (3.45 g) retention time of 12.35 min.

Provenance & Evidence