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

関与物質

反応条件

反応手順

DIPEA (71.9 μL, 0.412 mmol) was added to a solution of 6-chloro-5-(4-fluoro-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 5.1, 75 mg, 0.187 mmol) and (R)-pyrrolidin-3-ol (19.97 mg, 0.225 mmol) in iPrOH (187 μL) in a vial which was sealed and heated at 140° C. for 1 h. After cooling at RT, the RM was dissolved in EtOAc and washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2% to 10% MeOH) to afford the title compound as a white foam. HPLC (Condition 4) tR=4.73 min, UPLC-MS (Condition 3) tR=0.93 min, m/z=452.4 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.95 (m, 2H) 3.00 (d, J=11.34 Hz, 1H) 3.18-3.51 (m, 3H) 4.22 (br. s, 1H) 4.86 (br. s, 1H) 7.32 (d, J=8.60 Hz, 2H) 7.77-8.11 (m, 4H) 8.76 (br. s, 1H) 10.17 (s, 1H) 12.90 (br. s, 1H).

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