반응 #679530

반응 방정식

tert-butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate

Et2O

2,4-dichloro-5-(trifluoromethyl)pyrimidine

Et3N

→

title compound

tert-Butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

용매

DCE

t-BuOH

반응 조건

후처리

1. 1
   기타at room temperature
2. 2
   workup.ADDITIONAfter completion of the addition
3. 3
   workup.ADDITIONwere added
4. 4
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 48 hours
5. 5
   기타the volatiles were evaporated under reduced pressure
6. 6
   기타the resulting residue was purified
7. 7
   기타silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-55% EtOAc in petroleum benzine 40-60° C.)

실험 절차

A 1.0 M ZnCl2 solution in Et2O (1.14 mL, 1.14 mmol) was added cautiously to a stirred solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (217 mg, 0.999 mmol) in a 1:1 t-BuOH:DCE mixture (50 mL) at room temperature. After completion of the addition stirring was continued for 20 minutes then tert-butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate (I9) (263 mg, 0.952 mmol) followed by Et3N (0.159 mL, 1.14 mmol) were added. The resulting mixture was stirred at room temperature for 48 hours then the volatiles were evaporated under reduced pressure and the resulting residue was purified using silica gel column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-55% EtOAc in petroleum benzine 40-60° C.) to give the title compound K5 as a white solid (155 mg, 36%); 1H NMR (400 MHz, d6-DMSO) δ 10.75 (s, 1H), 8.82 (s, 1H), 8.73 (d, J=2.4 Hz, 1H), 8.00 (dd, J=8.5, 2.4 Hz, 1H), 7.30 (d, J=8.5 Hz, 1H), 4.11-4.01 (m, 2H), 2.93-2.75 (m, 3H), 1.81 (d, J=11.1 Hz, 2H), 1.63-1.50 (m, 2H), 1.41 (s, 9H). LCMS-A: rt 5.604 min; m/z 458, 460 [M+H]+.

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