1,2-Dichloroethane → HCID 86659193, compound

Participants

Reaction Steps

Into a 20 mL vial, cis-1-[6-chloro-2-(methylsulfonyl)-4-pyrimidinyl]-6-(trifluoromethyl)-3-piperidinecarboxylic acid (77 mg, 0.199 mmol) was dissolved in 1,4-dioxane (1 mL), and Hunig's base was added (0.14 mL, 0.794 mmol) followed by methylamine (0.199 mL, 0.397 mmol). The reaction mixture was stirred at room temperature overnight. Additional 100 uL of 2M methylamine in THF were added, and the reaction mixture was stirred at room temperature until LCMS analysis indicates>95% completion. The reaction was concentrated, then re-dissolved with DMF (2 mL), and added HOBT (60.8 mg, 0.397 mmol), EDC (57.1 mg, 0.298 mmol), N-methylmorpholine (0.109 mL, 0.993 mmol) and cyclopentylamine (0.029 mL, 0.298 mmol). The reaction was stirred at room temperature overnight. Water (15 mL) was added, and the resulting mixture was extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, dried (MgSO4), filtered, and concentrated. The resulting material was dissolved in 1 mL DMSO and purified on HPLC (HPLC condition: open-access Gilson using Unipoint software with a Varian Polaris 5u C18(2) 100A, 50×30.00 mm 5 micron. 10-minute run (30 ml/min, 40% CH3CN/H2O, 0.1% TFA to 60% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were pooled and concentrated and freeze-dried to afford the title compound (40 mg) as a white solid. LC-MS (ES) m/z=406 [M+H]+.

Provenance & Evidence