Trifluoroacetic acid → HCID 66990883, compound

Participants

Reaction Steps

To cis-1-[6-(3-amino-1H-indazol-6-yl)-2-({[2,4-bis(methyloxy)phenyl]methyl}amino)-4-pyrimidinyl]-N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (250 mg, 0.38 mmol) was added trifluoroacetic acid (TFA) (6 mL). After 3 hours, LCMS analysis indicated the reaction to be completed. The reaction mixture was concentrated under vacuum, and the resulting residue was co-evaporated from toluene (2×50 mL), then from CH3CN (50 mL). To the resulting pink solid was added a saturated aqueous NaHCO3 solution and EtOAc. The organic layer was separated, and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. This material was purified by flash chromatography (gradient: 100% CH2Cl2 to 90:10:1 CH2Cl2:CH3OH:NH4OH). The cleaner fractions were combined and concentrated under vacuum to afford a yellow solid. This material was dissolved in EtOAc (˜2 mL), and the resulting solution was transfered to a microwave vial. The vial was capped, and heated to 70 C. Hexane was added dropwise until the solution became cloudy, then the mixture was allowed to cool to room temperature. A spatula was used to scrap the solid, and the mixture was filtered. The collected pink solid was washed with hexanes and a white solid precipitate from the filtrate. This white solid was collected by filtration to afford the desired product (35 mg). LC-MS (ES) m/z=503 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.05-1.34 (m, 5H), 1.56 (m, 1H), 1.63-1.85 (m, 7H), 2.07 (m, 1H), 2.33, (m, 1H), 3.06 (bs, 1H), 3.53 (m, 1H), 5.39 (s, 2H), 6.29 (s, 2H), 6.78 (s, 1H), 7.63 (dd, J=8.5, 1.1 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.84 (d, J=7.9 Hz, 1H), 7.99 (s, 1H), 11.54 (s, 1H).

Provenance & Evidence