Trifluoroacetic acid → HCID 86679013, compound

Participants

Reaction Conditions

Reaction Steps

To a THF solution (2 mL) of the intermediate from Step A (227 mg, 0.521 mmol) at 0° C. was added trifluoroacetic acid (0.044 mL, 0.574 mmol) and tert-butyl nitrite (0.186 mL, 1.564 mmol). After stirring at 0° C. for 30 minutes, the mixture was concentrated in vacuo, ensuring that the temperature was maintained below 40° C. The residue was suspended in acetonitrile (3 mL), cooled to 0° C., and 3-aminopyridine (245 mg, 2.61 mmol) was added in one portion. The resultant mixture was heated to 40° C. for one hour, and then stirred at ambient temperature for 16 hours. The mixture was concentrated in vacuo, suspended in EtOAc and washed sequentially with water (4×), saturated aqueous ammonium chloride solution (2×), and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification by silica gel column chromatography using DCM/MeOH (with 0.5% NH4OH) gradient provided the title compound. Chiral separation using SFC on a Chiralpak IC column provided both enantiomers of the title compound, 1H NMR (500 MHz, DMSO-d6): δ 9.53 (1H, s), 9.05 (1H, dd, J=8.08, 1.58 Hz), 8.77 (1H, d, J=2.48 Hz), 8.63 (1H, dd, J=4.47, 1.58 Hz), 8.28 (1H, d, J=4.69 Hz), 8.00 (1H, d, J=8.47 Hz), 7.36 (2H, ddd, J=21.65, 8.21, 4.57 Hz), 6.86 (2H, s), 4.85-4.77 (2H, m), 3.06-2.95 (2H, m), 1.72 (3H, s). m/z=498.2 (M+H).

Provenance & Evidence