Triethylamine → tert-Butyl 3-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

Zinc chloride (1.0 M in Et2O) (4.83 mL, 4.83 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.769 g, 3.54 mmol) in 1:1 dichloroethane/tert-butanol (64 mL) at room temperature under nitrogen. After stirring for 10 minutes, tert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate (I7) (0.800 g, 3.22 mmol) was added followed by Et3N (1.08 mL, 7.73 mmol). The resulting mixture was stirred at room temperature for 20 hours then the volatiles removed in vacuo. Water was added to the solid residue and the resulting suspension sonicatated for 2 minutes. The suspension was filtered, and the filter cake dried then adsorbed onto silica gel and purified using column chromatography (CombiFlash Rf, 40 g SiO2 Cartridge, 10-40% EtOAc in cyclohexane) to give a white solid. The solid was suspended in MeOH (7 mL) and sonicated for 30 seconds. The resulting suspension was filtered and the filter cake was washed with MeOH (3 mL) then dried to give the title compound K4 as a white solid (0.777 g, 56%); 1H NMR (300 MHz, d6-DMSO) δ 10.6 (s, 1H), 8.79 (s, 1H), 7.66 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.4 Hz, 2H), 4.23 (t, J=7.6 Hz, 2H), 3.80 (s, 3H), 1.40 (s, 9H). LCMS-B: rt 8.810 min; m/z 429 [M+H]+.

1. stirringThe resulting mixture was stirred at room temperature for 20 hours
2. customthe volatiles removed in vacuo
3. additionWater was added to the solid residue
4. waitthe resulting suspension sonicatated for 2 minutes
5. filtrationThe suspension was filtered
6. customthe filter cake dried
7. custompurified
8. customto give a white solid
9. customsonicated for 30 seconds
10. filtrationThe resulting suspension was filtered
11. washthe filter cake was washed with MeOH (3 mL)
12. customthen dried

ORD-Eintrag

ord-2b821ddd7b8d4e549c7b34ae1170e0c6

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09238644B2