The excess of solvents was removed under reduced pressure. 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 Faldaprevir (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 Rabbit polyclonal to PCSK5 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 Faldaprevir 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 mixture stirred for 1?h at 90?C. After cooling, the reaction mixture 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 Faldaprevir 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 mixture was heated to reflux temperature for 12?h. After cooling to room temperature, the reaction mixture 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 mixture was heated to reflux temperature for 12?h. After cooling to room temperature, the reaction mixture 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, Faldaprevir 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 mixture was refluxed for 3?h then excess of solvents were removed under reduced pressure.