Propionyl chloride → 1-[4-(Cyanomethyl)-1-propanoylpiperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxamide

To a suspension of 4-[4-carbamoyl-3-(phenylamino)-1H-pyrazol-1-yl]-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-1) (50 mg, 0.11 mmol) in THF (1 mL) was added DIPEA (0.060 mL, 0.34 mmol), followed by propanoyl chloride (0.020 mL, 0.18 mmol). The resulting mixture was allowed to stir for 18 hours before the reaction mixture was concentrated in vacuo to afford an orange oil. The residue was dissolved in DMSO (2 mL) and purified by mass-triggered reverse phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the title compound, Example #33-1, as a colorless solid.

1. concentrationwas concentrated in vacuo
2. customto afford an orange oil
3. custompurified by mass-triggered reverse phase preparative HPLC (MeCN/water
4. additiondiluted with saturated aqueous NaHCO3
5. extractionextracted with EtOAc (2×)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORDレコード

ord-0466931882984dba9c29ae4e3fd53335

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09328099B2