Triethylamine → HCID 73659150, compound

Participants

Reaction Steps

A 250-mL round-bottomed flask was charged with 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (2.50 g, 6.23 mmol), 20 mL of CH2Cl2, triethylamine (3.47 mL, 24.93 mmol), and 6-chloropyridine-3-sulfonyl chloride (1.32 g, 6.23 mmol, Organic Process Research & Development 2009, 13, 875). After stirring at room temperature for 30 min, water was added and the layers were separated. The organics were dried (MgSO4), filtered, and concentrated to give an oily solid. To this material was added 10 mL of EtOH and concentrated ammonium hydroxide (9.95 mL, 255 mmol). The vessel was sealed and heated at 120° C. for 12 h. After the mixture was allows to cool to room temperature, EtOAc (100 mL) and water (50 mL) were added. The organics were separated, dried (MgSO4), filtered and concentrated to give an oil. Purification via column chromatography on silica gel (0 to 70% EtOAc in hexanes) delivered 2-(4-(4-((6-amino-3-pyridinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1.65 g) as an off-white solid. 1H NMR (400 MHz, CD3OD) δ=8.30 (d, J=2.3 Hz, 1H), 7.74 (dd, J=2.4, 8.9 Hz, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.00 (d, J=9.0 Hz, 2H), 6.64 (d, J=8.8 Hz, 1H), 3.35-3.30 (m, 4H), 3.17-3.11 (m, 4H). m/z (ESI, +ve ion) 484.9 (M+H)+. GK-GKRP IC50 (Binding)=0.085 μM; GK-GKRP EC50 (LC MS/MS-2)=0.142 μM.

Provenance & Evidence