丙烷-1-亚磺酸钠

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of preparation 25a (70 mg, 139 μmol), sodium 1-propylsulfinate (54 mg, 415 μmol), L-proline (20 mg, 174 μmol), CuI (7 mg, 37 μmol), K2CO3 (24 mg, 174 μmol) in DMSO (0.7 mL) is heated 60 min at 110° C. The reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.). Yield: 11 mg (15% of theory); ESI mass spectrum: [M+H]+=532; Retention time HPLC: 1.06 min (Z003—001). The reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.) 1.06 min (Z003—001)

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of preparation 25a (70 mg, 139 μmol), sodium 1-propylsulfinate (54 mg, 415 μmol), L-proline (20 mg, 174 μmol), CuI (7 mg, 37 μmol), K2CO3 (24 mg, 174 μmol) in DMSO (0.7 mL) is heated 60 min at 110° C. The reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.). Yield: 11 mg (15% of theory); ESI mass spectrum: [M+H]+=532; Retention time HPLC: 1.06 min (Z003—001). The reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.) 1.06 min (Z003—001)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 160 mg (0.55 mmol) of 2-bromo-N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-propionamide in DMF (3 mL) were added 87 mg (0.71 mmol) of 1-propanesulfinic acid sodium salt in one portion. Pyridine (48 μL) was added and the reaction was stirred at 50° C. for 18 h. The mixture was acidified with 1M aqueous HCl solution (1 mL) and extracted with diethyl ether (3×3 mL). The combined organic layers were dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography (silica, eluent heptanes, 0-20% ethyl acetate) to afford 86 mg of N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-2-(propane-1-sulfonyl)-propionamide. extracted with diethyl ether (3×3 mL) The combined organic layers were dried over Na2SO4 filtered The filtrate was concentrated under reduced pressure The crude material was purified by column chromatography (silica, eluent heptanes, 0-20% ethyl acetate)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 160 mg (0.55 mmol) of 2-bromo-N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-propionamide in DMF (3 mL) were added 87 mg (0.71 mmol) of 1-propanesulfinic acid sodium salt in one portion. Pyridine (48 μL) was added and the reaction was stirred at 50° C. for 18 h. The mixture was acidified with 1M aqueous HCl solution (1 mL) and extracted with diethyl ether (3×3 mL). The combined organic layers were dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography (silica, eluent heptanes, 0-20% ethyl acetate) to afford 86 mg of N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-2-(propane-1-sulfonyl)-propionamide. extracted with diethyl ether (3×3 mL) The combined organic layers were dried over Na2SO4 filtered The filtrate was concentrated under reduced pressure The crude material was purified by column chromatography (silica, eluent heptanes, 0-20% ethyl acetate)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Fluorobenzaldehyde (3.03 mL, 28.2 mmol) and sodium n-propylsulphinate (4.03 g, 31.0 mmol, synthesised as described in J. Med. Chem. 1989, 32, 2436) were dissolved in dry DMSO and the resulting solution heated at 100° C. for 18 h. The mixture was allowed to cool and then poured onto approximately 50 g of ice. After the ice had melted, the product was extracted into ethyl acetate (×2). The combined organic extracts were dried (MgSO4) and concentrated. Chromatography on silica eluting with 20 to 40% ethyl acetate in hexane afforded the product as a white solid (3.21 g, 54% yield). 1H NMR (400 MHz, CDCl3) 1.02 (3H, t, J=7.5 Hz), 1.72-1.82 (2H, m), 3.10-3.14 (2H, m), 8.07-8.11 (4H, m), 10.14 (1H, s). to cool the product was extracted into ethyl acetate (×2) The combined organic extracts were dried (MgSO4) concentrated

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of preparation 25a (70 mg, 139 μmol), sodium 1-propylsulfinate (54 mg, 415 μmol), L-proline (20 mg, 174 μmol), CuI (7 mg, 37 μmol), K2CO3 (24 mg, 174 μmol) in DMSO (0.7 mL) is heated 60 min at 110° C. The reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.). Yield: 11 mg (15% of theory); ESI mass spectrum: [M+H]+=532; Retention time HPLC: 1.06 min (Z003—001). The reaction mixture is purified by preparative reversed-phase HPLC (XBridge, gradient of methanol in water, 0.3% NH4OH, 60° C.) 1.06 min (Z003—001)