Diisopropylethylamine → (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

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(R)-Pyrrolidin-3-ol (17.1 ml, 211.2 mmol) and DIPEA (67.6 ml, 387.6 mmol) were added to a suspension of 5-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 2.3, 69.6 g, 175.9 mmol) in iPrOH (120 mL) and stirred at 140° C. for 1 h. The mixture was diluted with EtOAc (1 L), washed with 1N HCl (2×200 mL), a sat. solution of NaHCO3 (200 mL) and brine (2×200 mL) and dried over Na2SO4. The solvent was evaporated off under reduced pressure and the product was crystallized from EtOAc/iPr2O to afford the title compound as a white crystalline solid. HPLC (Condition 5) tR=6.58 min, UPLC-MS (Condition 6) m/z=446.0/448.0 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.78-2.01 (m, 2H) 3.55 (d, J=11.34 Hz, 1H) 3.64-3.76 (m, 1H) 3.79-3.91 (m, 2H) 4.33 (br. s, 1H) 4.97 (d, J=3.13 Hz, 1H) 7.33 (d, J=9.38 Hz, 2H) 7.83 (d, J=8.99 Hz, 2H) 8.30-8.36 (m, 1H) 8.66 (d, J=2.35 Hz, 1H) 10.20 (s, 1H).

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