For the simple derivatives, generally the 6-sulfamoyl derivatives were more effective CAIs compared to the corresponding 5-sulfamoyl ones (e.g. r.t. and extracted with EtOAc (3??5.0?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/1.8, 7.8), 7.96 (1H, d, 1.8), 9.97 (1H, s, exchange with D2O, N(ESI positive) 232.0 [M?+?H]+. Experimental in agreement with reported data41. 2-Aminobenzo[d]thiazole-6-sulfonamide (2) A suspension of 4-thioureido-benzenesulfonamide 1 (1.0?mmol, 1.0 eq) in CHCl3 (4.0?ml) was treated with Br2 (1.5 eq) drop-wise. The mixture was heated to 70?C for 4.5?h, cooled-down to r.t. and the solvents were removed under reduced pressure to give a solid that was dissolved in H2O (5.0?ml). The aqueous solution was treated with NH4OH and stirred at 90?C for 1?h. The formed precipitate was filtered-off, washed with H2O and dried under vacuum to afford the titled compound. White solid, 80% yield; 8.4), 7.69 (1H, dd, 8.4, 1.8), 7.89 (2H, s, exchange with D2O, N1.8); (ESI positive) 230.00 [M?+?H]+. Experimental in agreement with reported data41. 2-Aminobenzo[d]thiazole-5-sulfonamide (4) A suspension of 3 (1.2?g, 1.0 eq.) in CHCl3 (15.0?ml) was treated with Br2 (1.5 eq) in CHCl3 (1.0?ml) drop-wise. The mixture was heated to 70?C for 12?h, cooled down to r.t., the solvent eliminated in vacuum to give a residue that was dissolved in H2O (5.0?ml) and treated with NH4OH, followed by 1?h stirring at 90?C. The cooled reaction mixture was filtered, washed with water and dried under vacuum to afford the titled compound. White solid, 45% yield; 8.0), 7.49C7.56 (4H, m, 2H exchange with D2O, SO2N(ESI positive) 230.00 [M?+?H]+. 2-Amino-4-bromobenzo[d]thiazole-6-sulfonamide (5) A suspension of 2 (0.75?g, 1 eq) in chloroform (15.0?ml) was treated with a solution of Br2 (8.0 eq) in chloroform (2.5?ml) drop-wise. The mixture was heated to 70?C for 4?h. After cooling to r.t. the solvents were removed under reduced pressure. The obtained solid was dissolved in water (5.0?ml) and treated with ammonium hydroxide (pH =10), then the reaction mixture stirred for 1?h at 90?C. The precipitated solid was filtered under vacuum, washed with H2O (3??5.0?ml), then with (ESI positive) 307.9 [M?+?H]+. 2A suspension of 4 (0.2?g, 1.0 eq) in chloroform (4.0?ml) was treated with a solution of Br2 (6.0 eq) in chloroform (1.0?ml) drop-wise. The mixture was heated to 70?C for 12?h. After cooling to r.t. the solvents were removed under reduced pressure. The obtained solid was dissolved in water (5.0?ml) and treated with ammonium hydroxide (pH =10), then the reaction combination stirred for 1?h at 90?C. After chilling, the reaction combination was extracted with EtOAc (3??5?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/8.4), 7.66 (2H, s, exchange with D2O, SO2N8.4), 8.08 (2H, s, exchange with D2O, N(ESI negative) 305.7 [M-H]?. 2-Amino-4-iodobenzo[d]thiazole-6-sulfonamide (7) A solution of 2 (0.3?g, 1.0 eq) in methanol (3.0?ml) was treated with iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The combination was heated to reflux temp for 12?h. After chilling to room temp, the reaction combination was extracted with EtOAc (3??5.0?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/2.0), 8.16 (1H, d, 2.0), 8.21 (2H, s, exchange with D2O, N(ESI positive) 355.9 [M?+?H]+. 2-Amino-4-iodobenzo[d]thiazole-5-sulfonamide (8) A solution of 4 (0.2?g, 1.0 eq) in methanol (3.0?ml) was treated with a solution of iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The combination was heated to reflux temp for 12?h. After chilling to room temp, the reaction combination was extracted with EtOAc (3??5?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/8.0), 7.63 (2H, s, exchange with D2O, SO2N8.0), 8.03 (2H, s, exchange with D2O, N(ESI positive) 355.8 [M?+?H]+. N-(6-sulfamoylbenzo[d]thiazol-2-yl)acetamide (9) A solution of 2 (1.0?g, 1.0 eq) in acetic acid (2.0?ml) was cooled to 0?C followed by drop-wise addition of acetic anhydride (1.2 eq). The reaction combination was refluxed for 3?h then excess of solvents were removed under reduced pressure to obtain a residue which was washed with Et2O (3??5?ml) to obtain titled compound. White solid, 96% yield; 1.2), 8.50 (1H, t,.The combination was heated to 70?C for 4?h. combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/1.8, 7.8), 7.96 (1H, d, 1.8), 9.97 (1H, s, exchange with D2O, N(ESI positive) 232.0 [M?+?H]+. Experimental in agreement with reported data41. 2-Aminobenzo[d]thiazole-6-sulfonamide (2) A suspension of 4-thioureido-benzenesulfonamide 1 (1.0?mmol, 1.0 eq) in CHCl3 (4.0?ml) was treated with Br2 (1.5 eq) drop-wise. The combination was heated to 70?C for 4.5?h, cooled-down to r.t. and the solvents were removed under reduced pressure to give a solid that was dissolved in H2O (5.0?ml). The aqueous remedy was treated with NH4OH and stirred at 90?C for 1?h. The created precipitate was filtered-off, washed with H2O and dried under vacuum to afford the titled compound. White solid, 80% yield; 8.4), 7.69 (1H, dd, 8.4, 1.8), 7.89 (2H, s, exchange with D2O, N1.8); (ESI positive) 230.00 [M?+?H]+. Experimental in agreement with reported data41. 2-Aminobenzo[d]thiazole-5-sulfonamide (4) A suspension of 3 (1.2?g, 1.0 eq.) in CHCl3 (15.0?ml) was treated with Br2 (1.5 eq) in CHCl3 (1.0?ml) drop-wise. The combination was heated to 70?C for 12?h, cooled down to r.t., the solvent eliminated in vacuum to give a residue that was dissolved in H2O (5.0?ml) and treated with NH4OH, followed by 1?h stirring at 90?C. The cooled reaction combination was filtered, washed with water and dried under vacuum to afford the titled compound. White solid, 45% yield; 8.0), 7.49C7.56 (4H, m, 2H exchange with D2O, SO2N(ESI positive) 230.00 [M?+?H]+. 2-Amino-4-bromobenzo[d]thiazole-6-sulfonamide (5) A suspension of 2 (0.75?g, 1 eq) in chloroform (15.0?ml) was treated with a solution of Br2 (8.0 eq) in chloroform (2.5?ml) drop-wise. The combination was heated to 70?C for 4?h. After chilling to r.t. the solvents were removed under reduced pressure. The acquired solid was dissolved in water (5.0?ml) and treated with ammonium hydroxide (pH =10), then the reaction combination stirred for 1?h at CP-724714 90?C. The precipitated solid was filtered under vacuum, washed with H2O (3??5.0?ml), then with (ESI positive) 307.9 [M?+?H]+. 2A suspension of 4 (0.2?g, 1.0 eq) in chloroform (4.0?ml) was treated with a solution of Br2 (6.0 eq) in chloroform (1.0?ml) drop-wise. The combination was heated to 70?C for 12?h. After chilling to r.t. the solvents were removed under reduced pressure. The acquired solid was dissolved in water (5.0?ml) and treated with ammonium hydroxide (pH =10), then the reaction combination stirred for 1?h at 90?C. After chilling, the reaction combination was extracted with EtOAc (3??5?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/8.4), 7.66 (2H, s, exchange with D2O, SO2N8.4), 8.08 (2H, s, CP-724714 exchange with D2O, N(ESI negative) 305.7 [M-H]?. 2-Amino-4-iodobenzo[d]thiazole-6-sulfonamide (7) A solution of 2 (0.3?g, 1.0 eq) in methanol (3.0?ml) was treated with iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The combination was heated to reflux temp for 12?h. After chilling to room temp, the reaction combination was extracted with EtOAc (3??5.0?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/2.0), 8.16 (1H, d, 2.0), 8.21 (2H, s, exchange with D2O, N(ESI positive) 355.9 [M?+?H]+. 2-Amino-4-iodobenzo[d]thiazole-5-sulfonamide (8) A solution of 4 (0.2?g, 1.0 eq) in methanol (3.0?ml) was treated with a solution of iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The combination was heated to reflux temp for 12?h. After chilling to room temp, the reaction combination was extracted with EtOAc (3??5?ml). The combined organic layers were washed.The combination was heated to reflux temperature for 12?h. combination was cooled-down to r.t. and extracted with EtOAc (3??5.0?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified Rabbit Polyclonal to p47 phox (phospho-Ser359) by silica gel column chromatography eluting with EtOAc/1.8, 7.8), 7.96 (1H, d, 1.8), 9.97 (1H, s, exchange with D2O, N(ESI positive) 232.0 [M?+?H]+. Experimental in agreement with reported data41. 2-Aminobenzo[d]thiazole-6-sulfonamide (2) A suspension of 4-thioureido-benzenesulfonamide 1 (1.0?mmol, 1.0 eq) in CHCl3 (4.0?ml) was treated with Br2 (1.5 eq) drop-wise. The combination was heated to 70?C for 4.5?h, cooled-down to r.t. and the solvents were removed under reduced pressure to give a solid that was dissolved in H2O (5.0?ml). The aqueous remedy was treated with NH4OH and stirred at 90?C for 1?h. The created precipitate was filtered-off, washed with H2O and dried under vacuum to afford the titled compound. White solid, 80% yield; 8.4), 7.69 (1H, dd, 8.4, 1.8), 7.89 (2H, s, exchange with D2O, N1.8); (ESI positive) 230.00 [M?+?H]+. Experimental in agreement with reported data41. 2-Aminobenzo[d]thiazole-5-sulfonamide (4) A suspension of 3 (1.2?g, 1.0 eq.) in CHCl3 (15.0?ml) was treated with Br2 (1.5 eq) in CHCl3 (1.0?ml) drop-wise. The combination was heated to 70?C for 12?h, cooled down to r.t., the solvent eliminated in vacuum to give a residue that was dissolved in H2O (5.0?ml) and treated with NH4OH, followed by 1?h stirring at 90?C. The cooled reaction combination was filtered, washed with water and dried under vacuum to afford the titled compound. White solid, 45% yield; 8.0), 7.49C7.56 (4H, m, 2H exchange with D2O, SO2N(ESI positive) 230.00 [M?+?H]+. 2-Amino-4-bromobenzo[d]thiazole-6-sulfonamide (5) A suspension of 2 (0.75?g, 1 eq) in chloroform (15.0?ml) was treated with a solution of Br2 (8.0 eq) in chloroform (2.5?ml) drop-wise. The combination was heated to 70?C for 4?h. After chilling to r.t. the solvents were removed under reduced pressure. The acquired solid was dissolved in water (5.0?ml) and treated with ammonium hydroxide (pH =10), then the reaction combination stirred for 1?h at 90?C. The precipitated solid was filtered CP-724714 under vacuum, washed with H2O (3??5.0?ml), then with (ESI positive) 307.9 [M?+?H]+. 2A suspension of 4 (0.2?g, 1.0 eq) in chloroform (4.0?ml) was treated with a solution of Br2 (6.0 eq) in chloroform (1.0?ml) drop-wise. The combination was heated to 70?C for 12?h. After chilling to r.t. the solvents were removed under reduced pressure. The acquired solid was dissolved in water (5.0?ml) and treated with ammonium hydroxide (pH =10), then the reaction combination stirred for 1?h at 90?C. After chilling, the reaction combination was extracted with EtOAc (3??5?ml). The combined organic layers were washed with H2O (3??5.0?ml), dried over Na2SO4, filtered and concentrated to obtain a residue that was purified by silica gel column chromatography eluting with EtOAc/8.4), 7.66 (2H, s, exchange with D2O, SO2N8.4), 8.08 (2H, s, exchange with D2O, N(ESI negative) 305.7 [M-H]?. 2-Amino-4-iodobenzo[d]thiazole-6-sulfonamide (7) A solution of 2 (0.3?g, 1.0 eq) in methanol (3.0?ml) was treated with iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The combination was heated to reflux temp for 12?h. After chilling to room temp, the reaction combination was extracted with EtOAc (3??5.0?ml). The mixed organic layers had been cleaned with H2O (3??5.0?ml), dried more than Na2SO4, filtered and concentrated to secure a residue that was purified by silica gel column chromatography eluting with EtOAc/2.0), 8.16 (1H, d, 2.0), 8.21 (2H,.The combined organic levels were washed with H2O (3??5.0?ml), dried more than Na2SO4, filtered and concentrated to secure a residue that was purified by silica gel column chromatography eluting with EtOAc/1.8, 7.8), 7.96 (1H, d, 1.8), 9.97 (1H, s, exchange with D2O, N(ESI positive) 232.0 [M?+?H]+. thiocyanate (1.0 eq) at r.t. and heated to 90 then?C CP-724714 for 12?h. The response mix was cooled-down to r.t. and extracted with EtOAc (3??5.0?ml). The mixed organic layers had been cleaned with H2O (3??5.0?ml), dried more than Na2SO4, filtered and concentrated to secure a residue that was purified by silica gel column chromatography eluting with EtOAc/1.8, 7.8), 7.96 (1H, d, 1.8), 9.97 (1H, s, exchange with D2O, N(ESI positive) 232.0 [M?+?H]+. Experimental in contract with reported data41. 2-Aminobenzo[d]thiazole-6-sulfonamide (2) A suspension system of 4-thioureido-benzenesulfonamide 1 (1.0?mmol, 1.0 eq) in CHCl3 (4.0?ml) was treated with Br2 (1.5 eq) drop-wise. The mix was warmed to 70?C for 4.5?h, cooled-down to r.t. as well as the solvents had been removed under decreased pressure to provide a good that was dissolved in H2O (5.0?ml). The aqueous alternative was treated with NH4OH and stirred at 90?C for 1?h. The produced precipitate was filtered-off, cleaned with H2O and dried out under vacuum to cover the titled substance. White solid, 80% produce; 8.4), 7.69 (1H, dd, 8.4, 1.8), 7.89 (2H, s, exchange with D2O, N1.8); (ESI positive) 230.00 [M?+?H]+. Experimental in contract with reported data41. 2-Aminobenzo[d]thiazole-5-sulfonamide (4) A suspension system of 3 (1.2?g, 1.0 eq.) in CHCl3 (15.0?ml) was treated with Br2 (1.5 eq) in CHCl3 (1.0?ml) drop-wise. The mix was warmed to 70?C for 12?h, cooled off to r.t., the solvent removed in vacuum to provide a residue that was dissolved in H2O (5.0?ml) and treated with NH4OH, accompanied by 1?h stirring in 90?C. The cooled response mix was filtered, cleaned with drinking water and dried out under vacuum to cover the titled substance. White solid, 45% produce; 8.0), 7.49C7.56 (4H, m, 2H exchange with D2O, Thus2N(ESI positive) 230.00 [M?+?H]+. 2-Amino-4-bromobenzo[d]thiazole-6-sulfonamide (5) A suspension system of 2 (0.75?g, 1 eq) in chloroform (15.0?ml) was treated with a remedy of Br2 (8.0 eq) in chloroform (2.5?ml) drop-wise. The mix was warmed to 70?C for 4?h. After air conditioning to r.t. the solvents had been removed under decreased pressure. The attained solid was dissolved in drinking water (5.0?ml) and treated with ammonium hydroxide (pH =10), then your response mix stirred for 1?h in 90?C. The precipitated solid was filtered under vacuum, cleaned with H2O (3??5.0?ml), after that with (ESI positive) 307.9 [M?+?H]+. 2A suspension system of 4 (0.2?g, 1.0 eq) in chloroform (4.0?ml) was treated with a remedy of Br2 (6.0 eq) in chloroform (1.0?ml) drop-wise. The mix was warmed to 70?C for 12?h. After air conditioning to r.t. the solvents had been removed under decreased pressure. The attained solid was dissolved in drinking water (5.0?ml) and treated with ammonium hydroxide (pH =10), then your response mix stirred for 1?h in 90?C. After air conditioning, the response mix was extracted with EtOAc (3??5?ml). The mixed organic layers had been cleaned with H2O (3??5.0?ml), dried more than Na2SO4, filtered and concentrated to secure a residue that was purified by silica gel column chromatography eluting with EtOAc/8.4), 7.66 (2H, s, exchange with D2O, Thus2N8.4), 8.08 (2H, s, exchange with D2O, N(ESI bad) 305.7 [M-H]?. 2-Amino-4-iodobenzo[d]thiazole-6-sulfonamide (7) A remedy of 2 (0.3?g, 1.0 eq) in methanol (3.0?ml) was treated with iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The mix was warmed to reflux heat range for 12?h. After air conditioning to room heat range, the response mix was extracted with EtOAc (3??5.0?ml). The mixed organic layers had been cleaned with CP-724714 H2O (3??5.0?ml), dried more than Na2SO4, filtered and concentrated to secure a residue that was purified by silica gel column chromatography eluting with EtOAc/2.0), 8.16 (1H, d, 2.0), 8.21 (2H, s, exchange with D2O, N(ESI positive) 355.9 [M?+?H]+. 2-Amino-4-iodobenzo[d]thiazole-5-sulfonamide (8) A remedy of 4 (0.2?g, 1.0 eq) in methanol (3.0?ml) was treated with a remedy of iodine monochloride (4.0 eq) in methanol (1.0?ml) drop-wise. The mix was warmed to reflux heat range for 12?h. After air conditioning to room heat range, the response mix was extracted with EtOAc (3??5?ml). The mixed organic layers had been cleaned with H2O (3??5.0?ml), dried more than Na2SO4, focused and filtered to secure a residue that was purified by silica.