Diisopropylethylamine → 3-(2,5-Difluoro-4-(methylsulfonyl)phenoxy)-1'-(5-ethylpyrimidine-2-yl)-1,4'-bipiperidine-2-one

Temperature

120 °C

To a solution of 3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1,4′-bipiperidin-2-one HCl salt (64 mg, 0.15 mmol) and DIEA (0.080 mL, 0.45 mmol) in DMSO (2 mL) was added 2-chloro-5-ethylpyrimidine (26 mg, 0.18 mmol). The reaction was heated at 120° C. overnight. The reaction was cooled to ambient temperature and diluted with water (2 mL) and EtOAc (5 mL). The organic layer was separated and the aqueous washed with EtOAc. The combined organic layers were dried with MgSO4 and concentrated. The crude residue was purified by reverse phase HPLC (5 to 95% acetonitrile in water with 0.1% TFA). The combined fractions were concentrated to remove CH3CN and the pH adjusted to neutral by the addition of NaHCO3. The aqueous layer was extracted with EtOAc. The combined organic layers were dried with MgSO4 and concentrated to give 3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1′-(5-ethylpyrimidine-2-yl)-1,4′-bipiperidine-2-one (15 mg, 20%) as an off white solid. Mass spectrum (apci) m/z=495.2 (M+H).

1. temperatureThe reaction was cooled to ambient temperature
2. customThe organic layer was separated
3. washthe aqueous washed with EtOAc
4. dry with materialThe combined organic layers were dried with MgSO4
5. concentrationconcentrated
6. customThe crude residue was purified by reverse phase HPLC (5 to 95% acetonitrile in water with 0.1% TFA)
7. concentrationThe combined fractions were concentrated
8. customto remove CH3CN
9. additionneutral by the addition of NaHCO3
10. extractionThe aqueous layer was extracted with EtOAc
11. dry with materialThe combined organic layers were dried with MgSO4
12. concentrationconcentrated

ORD record

ord-b203ae07997749639149da066fab459c

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754226B2