Diethyl Ether → tert-Butyl 3-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Temperatur

0 °C

2,4-Dichloro-5-(trifluoromethyl)pyrimidine (0.355 g, 1.64 mmol) was stirred in a 1:1 t-BuOH:1,2-dichloroethane mixture (30 mL) at 0° C. and a 1.0 M ZnCl2 solution in diethyl ether (1.87 mL, 1.87 mmol) was added cautiously over 20 minutes and the reaction was left stirring at 0° C. for 30 minutes. A solution of tert-butyl 3-(4-aminophenyl)piperidine-1-carboxylate (I23) (0.431 g, 1.56 mmol) in 1:1 t-BuOH:1,2-dichloroethane (10 mL) was added drop-wise over 15 minutes at 0° C. followed by a solution of triethylamine (0.261 μL, 1.871 mmol) in 1:1 t-BuOH:1,2-dichloroethane (10 mL). The reaction was allowed to warm to room temperature and was stirred for 60 hours. Volatiles were evaporated in vacuo and the resulting oily residue was suspended in water (200 mL), the suspension was sonicated for 30 minutes and the product was collected by filtration, the solid was washed with water (5×10 mL) and dried under a high vacuum to give the title compound (I24) (0.638 g, 90% yield) as a pale pink solid; 1H NMR (400 MHz, d6-DMSO) δ 10.62 (s, 1H), 8.78 (s, 1H), 7.61 (d, J=8.5 Hz, 2H), 7.26 (d, J=8.6 Hz, 2H), 4.05-3.87 (m, 2H), 2.94-2.63 (m, 2H), 2.57 (ddd, J=11.2, 7.7, 3.7 Hz, 1H), 1.87 (d, J=12.8 Hz, 1H), 1.75-1.54 (m, 2H), 1.51-1.35 (m, 10H). LCMS Method C: rt 6.89 min; m/z 455.3 M−H]−.

1. waitthe reaction was left
2. temperatureto warm to room temperature
3. stirringwas stirred for 60 hours
4. customVolatiles were evaporated in vacuo
5. customthe suspension was sonicated for 30 minutes
6. filtrationthe product was collected by filtration
7. washthe solid was washed with water (5×10 mL)
8. customdried under a high vacuum

ORD-Eintrag

ord-ba15f26e47984be499a76d52e363cf28

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09421205B2