1,2-Dimethoxyethane → (S)-6-(3-Hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)nicotinamide

Participants

Reaction Steps

(S)-5-Bromo-6-(3-hydroxy-3-methylpyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 13.2, 60 mg, 0.130 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (85 mg, 0.261 mmol), Pd(PPh3)2Cl2 (10.98 mg, 0.016 mmol), Na2CO3 (55.3 mg, 0.521 mmol), DME (553 μL), water (158 μL) and EtOH (79 μL) were added to a MW vial, which was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 20 min. The RM was diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 54.3 mg, 0.078 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc, from 10% to 60% EtOAc) to yield the title compound as a colorless oil. UPLC-MS (Condition 3) tR=1.26 min, m/z=578.3 [M+H]+, m/z=622.3 [M+formic acid-H]−.

Provenance & Evidence