Ethyl Acetate → HCID 118195212, compound

Participants

Reaction Conditions

Reaction Steps

(R)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 171.1, 116 mg, 0.25 mmol) and 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (116 mg, 0.5 mmol) were dissolved in DME (1 mL). A solution of 2 M Na2CO3 (0.375 mL, 0.75 mmol) was added, the mixture was flushed with argon and PdCl2(dppf) (9 mg, 0.013 mmol) was added and the RM was stirred at 120° C. for 1 h. Additional 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (80 mg) and PdCl2(dppf) (9 mg, 0.013 mmol) were then added and the RM was stirred at 120° C. for further 45 min. After cooling at RT, the RM was treated with EtOAc, washed with brine dried over Na2SO4. The solvent was evaporated under reduced pressure to give a residue that was purified by flash chromatography (RediSep® Silica gel column, 12 g, EtOAc/2% MeOH in EtOAc, gradient 50 to 100% B, EtOAc/MeOH 10%) and treated with Si-Thiol (100 mg) in MeOH. The product was further purified by preparative SFC (Column Diol, from 21% to 26% in 6 min) to afford the title product as a beige foam. HPLC (Condition 4) tR=5.14 min, UPLC-MS (Condition 3) tR=0.98 min, m/z=479.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.66-1.94 (m, 2H) 2.89-3.00 (m, 1H) 3.14-3.23 (m, 1H) 3.23-3.42 (m, 3H) 4.20 (br. s, 1H) 4.88 (br. s, 1H) 7.34 (d, J=8.60 Hz, 2H) 7.47 (dd, J=9.78, 5.47 Hz, 1H) 7.81-7.90 (m, 2H) 8.05 (d, J=2.35 Hz, 1H) 8.62-8.79 (m, 2H) 8.81 (d, J=2.35 Hz, 1H) 10.17 (s, 1H).

Provenance & Evidence