1,2-Dichloroethane → HCID 86659194, compound

Participants

Reaction Steps

To cis-6-(trifluoromethyl)-3-piperidinecarboxylic acid (50 mg, 0.254 mmol) in THF (1.5 mL) into a 5 mL sealable vial were added molecular sieves, and the resulting mixture was stirred for 5 minutes. LiHMDS (0.888 mL, 0.888 mmol) was added dropwise, and the resulting mixture was stirred at room temperature for 2 minutes, then added 4,6-dichloro-2-(methylthio)pyrimidine (59.4 mg, 0.304 mmol). The reaction was check by LCMS after 5 minutes and observed a very clean conversion. The reaction was then stirred at room temperature for an additional 0.5 hours. Water (5 mL) was added followed by the dropwise addition of 1N HCl until the mixture became slightly acidic. The mixture was then extracted with EtOAc (3×10 mL), and the organics were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude oil was dissolved in DMF (1.5 mL), and then HOBT (78 mg, 0.507 mmol), EDC (58.3 mg, 0.304 mmol), and N-methylmorpholine (0.139 mL, 1.268 mmol) were added. The resulting mixture was stirred for 10 minutes. Benzylamine (0.033 mL, 0.304 mmol) was added, and the reaction mixture was stirred overnight at room temperature. LCMS of the reaction indicated clean conversion. To the reaction was added water (10 mL), and the resulting mixture was extracted with EtOAc (3×10 mL). The organics were then combined, washed with brine, dried over MgSO4, filtered and concentrated. The yellow oil was then purified on Biotage SNAP 10 g column gradient of 0 to 35% EtOAc in Hexanes over 30 minutes to afford the title compound (49 mg) as a clear oil. LC-MS (ES) m/z=445 [M+H]+.

Provenance & Evidence