Cesium carbonate → benzyl (1S,5S)-6-(5-cyano-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

The product of Example 52D (830 mg, 3.58 mmol) in toluene (20 mL) was treated with Pd2(dba)3 (71.0 mg, 0.072 mmol), BINAP (134 mg, 0.214 mmol), Cs2CO3 (2.32 g, 7.16 mmol) and 3-bromo-5-cyanopyridine (0.98 g, 5.37 mmol). The mixture was heated at 100° C. under N2 for 10 hours and then allowed to cool to room temperature and diluted with ethyl acetate (100 mL). The brown solution was washed with water (2×10 mL) and concentrated under reduced pressure. The residue was purified by chromatography (SiO2, EtOAc:hexane, 50:50, Rf. 0.3) to provide the title compound (770 mg, 64% yield). 1H NMR (MeOH-d4, 300 MHz) δ3.2(dd, J=12.9, 4.Hz, 1H), 3.30-3.4(m, 2H), 3.6(dd, J=8.2, 3.Hz, 1H), 3.96-4.10 (m, 3H), 4.74 (dd, J=6.1, 4.0 Hz, 1H), 5.10 (m, 2H), 7.15 (dd, J=2.7, 1.7 Hz, 1H), 7.25 (m, 3H), 7.35 (m, 2H), 7.96 (d, J=2.7 Hz, 1H), 8.15 (d, J=1.7 Hz, 1H); MS (DCI/NH3) m/z 335 (M+H)+.

Provenance & Evidence