2,2,2-Trifluoroethanol → 2,2,2-Trifluoroethyl 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

To a solution of 2,2,2-trifluoroethanol (15 mg, 0.15 mmol) in acetonitrile (1.0 mL) was added TEA (0.043 mL, 0.31 mmol) followed by N,N′-disuccinimidyl carbonate (59 mg, 0.23 mmol). The resulting mixture was allowed to stir at ambient temperature for 4 hours. A solution of 4-{4-carbamoyl-3-[(2-fluoropyridin-4-yl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-4) (70 mg, 0.15 mmol) and TEA (0.043 mL, 0.31 mmol) in DMSO (1.0 mL) was then added to the reaction mixture dropwise. The resulting mixture was heated to 50° C. and allowed to stir for 16 hours. The crude reaction mixture was cooled to ambient temperature and purified directly by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound, Example #30-1.

1. temperatureThe resulting mixture was heated to 50° C.
2. stirringto stir for 16 hours
3. customThe crude reaction mixture
4. temperaturewas cooled to ambient temperature
5. custompurified directly by reverse-phase preparative HPLC (MeCN/water
6. concentrationconcentrated in vacuo

ORDレコード

ord-fa420e99ee4941bd938942298c08621e

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09328099B2