3-Nitrophenylboronic Acid → 1-[5-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-pyrrolidin-3-ol

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Reaction Conditions

Reaction Steps

To 5-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-2-fluoro-pyridine (P-456, 0.3 g, 0.87 mmol) and 3-pyrrolidinol (2) (0.15 g, 1.74 mmol) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0.66 g, 4.34 mmol). The reaction mixture was stirred and heated at 100° C. for 2.5 h, cooled to room temperature, diluted with dichloromethane (8 mL), washed with 0.5 N HCl (2×4 mL), dried with Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using 5% methanol in dichloromethane to afford 0.27 g (75%) of P-601 as white solid. 1H NMR (DMSO-d6, 400 MHz): 7.95 (s, 1H), 7.2-7.46 (m, 6H), 6.91 (d, J=8.4 Hz, 1H), 6.35 (d, J=8.4 Hz, 1H), 4.9 (d, J=3.6 Hz, 1H), 4.32-4.4 (m, 1H), 3.76 (s, 2H), 3.71 (s, 3H), 3.12-3.45 (m, 4H), 1.8-2.05 (m, 2H) ppm; MS (APCI+): 413.1 (M+1), LC-MS: 91.6%.

Provenance & Evidence