반응 #679656

반응 방정식

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

Et2O

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

NEt3

→

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 addition the mixture
3. 3
   workup.ADDITION(500 mg, 1.80 mmol) was added
4. 4
   workup.STIRRINGthe mixture was stirred at room temperature for 44 hours
5. 5
   기타The organic solvents were evaporated to dryness
6. 6
   기타sonicated for 10 minutes
7. 7
   기타The solid was isolated by filtration
8. 8
   세척washed with water (2×100 mL)
9. 9
   기타air-dried
10. 10
    기타to give a cream solid
11. 11
    기타purified by silica gel column chromatography (40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

실험 절차

2,4-Dichloro-5-(trifluoromethyl)pyrimidine (411 mg, 1.89 mmol) was stirred in 1:1 t-BuOH:DCE (100 mL) at room temperature. A 1.0 M ZnCl2 solution in Et2O (2.16 mL, 2.16 mmol) was added cautiously and after addition the mixture was stirred at room temperature for 20 minutes. tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate I9 (500 mg, 1.80 mmol) was added followed by NEt3 (0.30 mL, 2.16 mmol) and the mixture was stirred at room temperature for 44 hours. The organic solvents were evaporated to dryness and the crude tan solid was suspended in water (250 mL) and sonicated for 10 minutes. The solid was isolated by filtration, washed with water (2×100 mL) and air-dried to give a cream solid. The solid was adsorbed onto silica and purified by silica gel column chromatography (40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A70 as an off white solid (346 mg, 42%). LCMS-A: rt 5.949 min; m/z 458 [M+H]+.

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