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

A mixture of (R)-5-bromo-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 13.2, 100 mg, 0.215 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (104 mg, 0.321 mmol), Pd(PPh3)2Cl2 (15.2 mg, 0.022 mmol), Na2CO3 (91 mg, 0.862 mmol), DME (914 μL), water (261 μL) and EtOH (131 μL) in a MW vial was sealed, evacuated/purged 3 times with argon and subjected to MW irradiation at 125° C. for 20 min. The RM was diluted with DME (3 mL), then stirred overnight with Si-Thiol (Silicycle 1.44 mmol/g, 90 mg, 0.129 mmol). The mixture was centrifuged and the supernatant was filtered through a 0.45 μm PTFE filter and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column DEAP, from 15% to 20% in 6 min) to yield the title compound as a yellow transparent oil. UPLC-MS (Condition 3) tR=1.28 min, m/z=581.2 [M+H]+, m/z=580.4 [M−H]−.

1. customwas sealed
2. customevacuated/purged 3 times with argon
3. customsubjected to MW irradiation at 125° C. for 20 min
4. additionThe RM was diluted with DME (3 mL)
5. filtrationthe supernatant was filtered through a 0.45 μm PTFE
6. filtrationfilter
7. customthe solvent was evaporated off under reduced pressure
8. customto give a residue which
9. customwas purified by preparative SFC (Column DEAP, from 15% to 20% in 6 min)

ORDレコード

ord-d7d5b46400a74f7986c4f8af77e51ae9

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08829195B2