Lithium Hexamethyldisilazide → 1-tert-Butylpiperidin-4-amine

Temperature

0 °C

A solution of LHMDS (1.0M in THF, 0.2 mL) was added to methyl 1-tert-butylpiperidine-4-carboxylate (31 mg, 0.16 mmol) in 2 mL THF at −78° C. After 20 minutes the solution was warmed to 0° C. and stirred for an additional 10 minutes. 7-Chloro-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-1,8-naphthyridin-2(1H)-one (COMPOUND BBB2) (28.5 mg, 0.063 mmol) was added and the reaction mixture stirred at 45° C. for 30 min. The solution was cooled to rt and quenched with saturated NH4Cl. The mixture was then partitioned between water and ethyl acetate. The organic phase was washed with water, brine and dried over magnesium sulfate. The filtered solution was concentrated and the residue purified by preparative silica gel thin layer chromatography using CHCl3/MeOH/NH4OH (87/12/1) as eluent to give the title compound. Mass spectrum (ESI) 616 (M+1). (Methyl 1-tert-butylpiperidine-4-carboxylate was prepared from 1-tert-butylpiperidin-4-one (COMPOUND PPA-1) by a procedure analogous to that described by Street, L. J.; et al J. Med. Chem. 1990, 33, 2690.)

1. stirringthe reaction mixture stirred at 45° C. for 30 min
2. temperatureThe solution was cooled to rt
3. customquenched with saturated NH4Cl
4. customThe mixture was then partitioned between water and ethyl acetate
5. washThe organic phase was washed with water, brine
6. dry with materialdried over magnesium sulfate
7. concentrationThe filtered solution was concentrated
8. customthe residue purified by preparative silica gel thin layer chromatography

ORD record

ord-9c2f22d08df249c88e0b4a192becef58

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06809199B2