Sodium bis(trimethylsilyl)amide → (R)-4-((R)-1-(6-chloro-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Under Ar, NaHMDS (1.0 M in THF, 0.96 mL, 0.96 mmol) was added over 30 s to a solution of (R)-4-((R)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.04 (255 mg, 0.968 mmol) in DMF (3 mL). After stirring 10 min, the resulting mixture was added over ca. 45 s to a cooled (−20° C.) solution of 6-chloro-3-(difluoromethyl)-4-(methylsulfonyl)-3H-imidazo[4,5-c]pyridine (215 mg, 0.763 mmol) in DMF (3 mL). After stifling 15 min, the reaction was quenched with saturated NH4Cl (3 mL) and was diluted with EtOAc (20 mL) and water (20 mL). The phases were separated, and the organic layer was washed with water (30 mL) and brine (30 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (20-45% acetone in hexanes) to provide (R)-4-((R)-1-(6-chloro-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one. LCMS-ESI+ (m/z): [M+H]+ calcd for C22H24ClF2N4O3: 465.2; found: 464.9.

1. additionthe resulting mixture was added over ca. 45 s to
2. waitAfter stifling 15 min
3. customthe reaction was quenched with saturated NH4Cl (3 mL)
4. additionwas diluted with EtOAc (20 mL) and water (20 mL)
5. customThe phases were separated
6. washthe organic layer was washed with water (30 mL) and brine (30 mL)
7. dry with materialThe organic phase was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude residue was purified by silica gel chromatography (20-45% acetone in hexanes)

ORD record

ord-15dde4ae20d647b6b5a9db515d264f29

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2