4-Ethynylbenzenesulfonamide

To a solution OF 4- [ (TRIMETHYLSILYL) ETHYNYL] BENZENESULFONAMIDE prepared as in Step 1 (1.69 g, 3.13 mmole) in anhydrous THF under A N2 atmosphere was added TBAF (10 mL-1.0 M in THF, 10 mmole) and the resulting mixture was stirred at room temperature. When silica TLC (1: 1 hexanes: EtOAc) indicated the reaction was complete, 10percent HC1 and EtOAc were added. The EtOAc layer was separated, washed twice with H20, aqueous NH4C1, dried over NA2S04 and concentrated IN VACUO to give 0. 748 g (62percent yield) of the product: ESHRMS M/Z 199.0506 (M+NH4, CGH7NO2SNH4, Calc'd 199. 0541).The crude intermediate 1 was treated with TBAF in THF (20 mL. 20 mmol) and stirred for 2 hours at r.t. then quenched by water and extracted with EtOAc (50 mL x 2). The combine organic layer was dried over anhydrous Na2SO4 concentrated to give crude intermediate 2 which was purified by column chromatography to give pure intermediate 2 (1.5 g, 84percent) as yellow solid.The crude intermediate 1 was treated with TBAF in THF (20 mL, 20 mmol) and stirred for 2 h at r.t., then quenched by water and extracted with EtOAc (50 mL×2). The combine organic layer was dried over anhydrous Na[0477] To a solution OF 4- [ (TRIMETHYLSILYL) ETHYNYL] BENZENESULFONAMIDE prepared as in Step 1 (1.69 g, 3.13 mmole) in anhydrous THF under A N2 atmosphere was added TBAF (10 mL-1.0 M in THF, 10 mmole) and the resulting mixture was stirred at room temperature. When silica TLC (1: 1 hexanes: EtOAc) indicated the reaction was complete, 10% HC1 and EtOAc were added. The EtOAc layer was separated, washed twice with H20, aqueous NH4C1, dried over NA2S04 and concentrated IN VACUO to give 0. 748 g (62% yield) of the product: ESHRMS M/Z 199.0506 (M+NH4, CGH7NO2SNH4, Calc'd 199. 0541).The crude intermediate 1 was treated with TBAF in THF (20 mL. 20 mmol) and stirred for 2 hours at r.t. then quenched by water and extracted with EtOAc (50 mL x 2). The combine organic layer was dried over anhydrous Na2SO4 concentrated to give crude intermediate 2 which was purified by column chromatography to give pure intermediate 2 (1.5 g, 84%) as yellow solid.The crude intermediate 1 was treated with TBAF in THF (20 mL, 20 mmol) and stirred for 2 h at r.t., then quenched by water and extracted with EtOAc (50 mL×2). The combine organic layer was dried over anhydrous Na2SO4, concentrated to give crude intermediate 2, which was purified by column chromatography to give pure intermediate 2 (1.5 g, 84%) as yellow solid. 1H NMR (300 MHz, DMSO-d6) delta7.82 (d, 2H), 7.68 (d, 2H), 7.46 (s, 2H), 4.45 (s, To a solution of 4-((trimethylsilyl)ethynyl)benzenesulfonamide (1.8 g, 7.1 15 mmol, Intermediate 70) in mixture of chloroform (10 mL) and methanol (10 mL), potassium carbonate (393 mg, 2.844 mmol) was added at 27 C and stirred at 27 C for 16 h. Upon completion, the reaction mixture was evaporated under reduced pressure. The residue was diluted with ethyl acetate (200 mL) and washed with 1 N HCI (150 mL). The organic layer was dried over Na2S04, filtered and the filtrate was evaporated under reduced pressure to afford 4-ethynylbenzenesulfonamide (1 .4 g, crude) as a brown solid.1H NMR (400 MHz, DMSO-d6) delta 7.82 (d, J = 8.3 Hz, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.44 (s, 2H), 4.42 (s, 1 H). MS m/z [M-H]= 179.97.General procedure: 2) 3-Ethynylbenzenesulfonamide Under cooling in an ice bath, potassium carbonate (610 mg) was added to a tetrahydrofuran (30 mL) and methanol (70 mL) solution of 3-[(trimethylsilyl)ethynyl]benzenesulfonamide (11.1 g), and the obtained solution was then stirred at a room temperature for 12 hours. Thereafter, water was added to the reaction solution, and the solvent was then distilled away under a reduced pressure. Then, the residue was extracted with diethyl ether. The organic layer was washed with water and a saturated saline, and was then dried over anhydrous magnesium sulfate, followed by vacuum concentration. The residue was purified by column chromatography (silica gel 60N, hexane:ethyl acetate=2:1 to 1:1), so as to obtain the title compound (5.84 g) in the form of a light brown solid. 1H NMR (600 MHz, DMSO-d6) delta ppm 4.36 (s, 1H) 7.42 (s, 2H) 7.57 (t, J=7.80 Hz, 1H) 7.67 (dt, J=7.79, 1.38 Hz, 1H) 7.81 (dt, J=7.91, 1.55 Hz, 1H) 7.85 (t, J=1.60 Hz, 1H); MS (ESI neg.) m/z: 180 [M-H]-General procedure: THF / methanol mixed solution (10 mL, 15.0 mL) of the compound of Reference Example 48 (584 mg) in was added potassium carbonate (843 mg), and stirred at room temperature for 2 hours. After completion of the reaction, and extracted with ethyl acetate by the addition of water. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, vacuum filtered and concentrated, the resulting residue was purified by silica gel column chromatography (n- hexane / ethyl acetate) to give the title compound (324 mg) was obtained.General procedure: Ketone 2a (50.2 mg, 0.25 mmol, 1.0 equiv.) andp-toluensulfonyl hydrazide (56.1 mg, 0.30 mmol, 1.2 equiv.) were dissolved in MeOH (4 mL). A drop ofHCl was added to the mixture, which was then refluxed for 3 h. Then, the mixture was cooled to rt andthe solvent was evaporated in vacuo. To this mixture, the terminal alkyne 3a (60.3 mg, 0.50 mmol, 2.0equiv.) and K2CO3 (69.4 mg, 0.50 mmol, 2.0 equiv.) were added and the mixture was dissolved indioxane (4 mL). The system was heated at 110 C for 12 h. The crude reaction was cooled down to rt, thesolvent was eliminated in vacuo and a NaHCO3 sat. aq. sol. and AcOEt were added. The layers wereseparated. The aqueous phase was extracted three times with AcOEt. The combined organic layers werewashed with NaHCO3 sat. aq. sol., brine, dried over Na2SO4 and filtered. Solvent was removed underreduced pressure. Finally product was purified by flash column chromatography on silica gel(Petrolether:AcOEt 2:8).General procedure: Ketone 2a (50.2 mg, 0.25 mmol, 1.0 equiv.) andp-toluensulfonyl hydrazide (56.1 mg, 0.30 mmol, 1.2 equiv.) were dissolved in MeOH (4 mL). A drop ofHCl was added to the mixture, which was then refluxed for 3 h. Then, the mixture was cooled to rt andthe solvent was evaporated in vacuo. To this mixture, the terminal alkyne 3a (60.3 mg, 0.50 mmol, 2.0equiv.) and K2CO3 (69.4 mg, 0.50 mmol, 2.0 equiv.) were added and the mixture was dissolved indioxane (4 mL). The system was heated at 110 C for 12 h. The crude reaction was cooled down to rt, thesolvent was eliminated in vacuo and a NaHCO3 sat. aq. sol. and AcOEt were added. The layers wereseparated. The aqueous phase was extracted three times with AcOEt. The combined organic layers werewashed with NaHCO3 sat. aq. sol., brine, dried over Na2SO4 and filtered. Solvent was removed underreduced pressure. Finally product was purified by flash column chromatography on silica gel(Petrolether:AcOEt 2:8).General procedure: Ketone 2a (50.2 mg, 0.25 mmol, 1.0 equiv.) andp-toluensulfonyl hydrazide (56.1 mg, 0.30 mmol, 1.2 equiv.) were dissolved in MeOH (4 mL). A drop ofHCl was added to the mixture, which was then refluxed for 3 h. Then, the mixture was cooled to rt andthe solvent was evaporated in vacuo. To this mixture, the terminal alkyne 3a (60.3 mg, 0.50 mmol, 2.0equiv.) and K2CO3 (69.4 mg, 0.50 mmol, 2.0 equiv.) were added and the mixture was dissolved indioxane (4 mL). The system was heated at 110 C for 12 h. The crude reaction was cooled down to rt, thesolvent was eliminated in vacuo and a NaHCO3 sat. aq. sol. and AcOEt were added. The layers wereseparated. The aqueous phase was extracted three times with AcOEt. The combined organic layers werewashed with NaHCO3 sat. aq. sol., brine, dried over Na2SO4 and filtered. Solvent was removed underreduced pressure. Finally product was purified by flash column chromatography on silica gel(Petrolether:AcOEt 2:8).To a solution of To a solution of

Molecular Weight:181.21
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:181.01974964
Monoisotopic Mass:181.01974964
Topological Polar Surface Area:68.5
Heavy Atom Count:12
Complexity:285
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes