Methanesulfonyl chloride → HCID 56932630, compound

Participants

Reaction Steps

To a solution of 2-(3-(3-amino-1-propyn-1-yl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol trifluoroacetate (102 mg, 0.17 mmol, Example 159) in CH2Cl2 (4 mL) was added diisopropylethylamine (89 μL, 0.51 mmol) and methanesulfonyl chloride (14 μL, 0.19 mmol). The reaction mixture was stirred at room temperature for 20 min and then partitioned between CH2Cl2 (5 mL) and saturated aqueous sodium bicarbonate (5 mL). The layers were separated, the organic material was separated, washed with saturated aqueous sodium bicarbonate (5 mL), dried (Na2SO4), filtered, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by column chromatography (12 g of silica gel, 10% to 50% EtOAc in hexanes) to provide N-(3-(2-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-2-propyn-1-yl)methanesulfonamide (57 mg) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.72 (br s, 1H), 8.09 (br s, 1H), 7.48-7.78 (m, 4H), 7.32 (br s, 1H), 7.11 (d, J=7.63 Hz, 1H), 4.07 (br s, 2H), 3.41-3.32 (m., 4H), 3.21-3.05 (m, 4H), 2.93 (s, 3H); m/z (ESI, +ve ion) 606.0 (M+H)+. GK-GKRP IC50 (Binding)=0.783 μM. GK-GKRP EC50 (LC MS/MS-2)=0.412 μM.

Provenance & Evidence