Diisopropylethylamine → 4-Phenyl-pyrazole-1-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

A mixture of 4-phenyl-1H-pyrazole hydrochloride (70 mg, 0.387 mmol), DIPEA (100 mg, 0.81 mmol) and DCM (5 mL) was added to a stirred solution of triphosgene (36 mg, 0.12 mmol) in DCM (2 mL) at room temperature. After 30 minutes, to the above solution, a mixture of 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared by method used for the synthesis of Intermediate 15) 118 mg, 0.3875 mmol), DIPEA (100 mg, 0.81 mmol) and DCM (5 mL) was added and the resulting mixture was stirred at room temperature for 1 hr. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure The residue was purified by preparative HPLC to afford 60 mg (17.6% Yield) of 4-phenyl-pyrazole-1-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]++: 439.15, 93.19%. 1H NMR (300 MHz, DMSO-d6): δ 8.8 (s, 1H), 8.4 (t, 1H), 8.35-8.3 (s, 1H), 7.8-7.72 (d, 2H), 7.48-7.38 (m, 3H), 7.35-7.24 (m, 3H), 7.0 (t, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.8-3.6 (m, 2H), 3.6-3.4 (m, 2H), 2.1-1.8 (m, 2H), 1.8-1.6 (m, 2H).

1. customprepared by method
2. additionwas added
3. extractionthe product was extracted with EtOAc
4. washthe organic layer was washed with brine
5. dry with materialThe organic phase was dried over Na2SO4
6. concentrationconcentrated under reduced pressure The residue
7. customwas purified by preparative HPLC

ORD record

ord-1aa6dde2f1404574ae75ed7a98c19c07

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129376B2