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

A 1.0 M solution of ZnCl2 in Et2O (22.5 mL, 22.5 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (4.48 g, 20.7 mmol) in t-BuOH (50 mL) and DCE (50 mL) and the mixture was stirred for 10 minutes. The mixture was diluted with t-BuOH (50 mL) and DCE (50 mL) before tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate (5.00 g, 18.8 mmol) and Et3N (3.14 mL, 22.5 mmol) were added. Stirring was continued overnight and the volatiles were subsequently removed in vacuo. The resultant residue was suspended in acetone (50 mL) then water (500 mL) and sonicated for 15 minutes before the solid was removed by vacuum filtration and the filter cake washed with water (100 mL). The solid was suspended in acetone (25 mL), filtered and the filter cake was washed with petroleum benzine 40-60° C. (200 mL) to give the title compound K8 as a light pink solid (6.57 g, 78%). LCMS-D: rt 3.618 min; m/z 445.1 [M−H]−.

1. additionwere added
2. stirringStirring
3. waitwas continued overnight
4. customthe volatiles were subsequently removed in vacuo
5. customwater (500 mL) and sonicated for 15 minutes before the solid
6. customwas removed by vacuum filtration
7. washthe filter cake washed with water (100 mL)
8. filtrationfiltered
9. washthe filter cake was washed with petroleum benzine 40-60° C. (200 mL)

ORD record

ord-ab16ab0db26040e691d0421d4e0843eb

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238644B2