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 diethyl ether (20.7 mL, 20.7 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (4.48 g, 20.7 mmol) in t-BuOH (100 mL) and DCE (100 mL). The mixture was stirred for 10 minutes then diluted with t-BuOH (100 mL) and DCE (100 mL) before tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate (5.00 g, 18.8 mmol) and Et3N (10.4 mL) were added. The mixture was stirred at room temperature overnight, the volatiles were removed in vacuo and the resultant residue was suspended in water (500 mL) and sonicated for 15 minutes. The solid was isolated by vacuum filtration and the filter cake washed with water (100 mL) and acetone (25 mL) to give the title compound (A133) as a tan solid (5.92 g, 71%); LCMS-A: rt 6.895 min; m/z 445.1 [M−H]−.

1. additionwere added
2. stirringThe mixture was stirred at room temperature overnight
3. customthe volatiles were removed in vacuo
4. customsonicated for 15 minutes
5. customThe solid was isolated by vacuum filtration
6. washthe filter cake washed with water (100 mL) and acetone (25 mL)

ORD record

ord-5f8ab7776bd341a9932aef13c0e269cc

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266864B2