N-bromobutanimide → 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine

Temperature

0 °C

To 5-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine/acetonitrile solution (1.4 g, 7.85 mmol/30 mL) at 0-5° C. was added portionwise NBS (1.4 g, 7.85 mmol) with internal temperature controlled below 5° C. The resulting mixture was stirred at 0° C. for 1 hour 40 min. The reaction mixture was concentrated under reduced pressure, and the residue was triturated with dilute aqueous NaOH/H2O (1 g/30 mL). The solid suspension was collected via filtration. The filtercake was washed with ice cold water (˜10 mL), and the filtrates were combined, and extracted with EtOAc (20 mL). The EtOAc extract was washed with brine (20 mL), dried over Na2SO4, and concentrated. A light yellow solid was combined with the filter cake, and dried under high vacuum as crude 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine. LCMS (m/z) 257.1/259.1 (MH+) 0.39 min. 1H NMR (CDCl3) δ ppm 7.90 (d, J=1.6 Hz, 1H), 7.54 (d, J=2.0 Hz, 1H), 4.80 (br. s., 1H), 4.12-4.02 (m, 2H), 3.54-3.44 (m, 2H), 2.71-2.61 (m, 1H), 1.78-1.68 (m, 4H).

1. customcontrolled below 5° C
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customthe residue was triturated with dilute aqueous NaOH/H2O (1 g/30 mL)
4. filtrationThe solid suspension was collected via filtration
5. washThe filtercake was washed with ice cold water (˜10 mL)
6. extractionextracted with EtOAc (20 mL)
7. extractionThe EtOAc extract
8. washwas washed with brine (20 mL)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. dry with materialdried under high vacuum as crude 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine
12. customLCMS (m/z) 257.1/259.1 (MH+) 0.39 min

ORD record

ord-b4605ab9482d4b2f807224d422d3e094

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242996B2