* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1944, vol. 17, p. 508,510, 512[2] Chem.Abstr., 1945, p. 4061
21
[ 63-74-1 ]
[ 122-79-2 ]
[ 144-80-9 ]
Reference：
[1] Monatshefte fuer Chemie, 1956, vol. 87, p. 47,59
[2] Yakugaku Zasshi, 1951, vol. 71, p. 1395,1397[3] Chem. Zentralbl., 1952, vol. 123, p. 8095
[4] Yakugaku Zasshi, 1952, vol. 72, p. 426,430[5] Chem. Zentralbl., 1953, vol. 124, p. 1633
22
[ 79-20-9 ]
[ 63-74-1 ]
[ 144-80-9 ]
Reference：
[1] Monatshefte fuer Chemie, 1956, vol. 87, p. 47,59
23
[ 108-24-7 ]
[ 63-74-1 ]
[ 144-80-9 ]
Reference：
[1] Patent: US2666073, 1952, ,
24
[ 63-74-1 ]
[ 1576-43-8 ]
Reference：
[1] Journal of Labelled Compounds and Radiopharmaceuticals, 2002, vol. 45, # 9, p. 763 - 774
25
[ 63-74-1 ]
[ 3119-02-6 ]
Yield
Reaction Conditions
Operation in experiment
60%
With hydrogenchloride; copper(ll) sulfate pentahydrate; sodium nitrite In water at 0 - 80℃;
A cold solution of NaNO2 (1.2 g, 17 mmol) was added to a suspension of sulfanilamide (2.5 g, 15 mmol) in 20 mL of a 2.3 N HCl solution at 0 °C with vigorous stirring. The resultant solution was poured into a suspension of KCN (4.16 g, 64 mmol) and CuSO4·5H2O (3.85 g, 15 mmol) in 20 mL of water. After stirring for 30 min, the solution was heated to 80 °C and then chilled. The precipitate was filtered, dried and extracted with 5percent ethanol in benzene Soxhelt apparatus. The organic extract was concentrated and the solid recrystallized from water to afford p-cyanobenzenosulfonamide (1.6 g, 60percent). m.p. 173.2 °C determined by thermogravimetry measures (TG-DT) and by melting point.
Reference：
[1] Journal of Molecular Structure, 2012, vol. 1024, p. 110 - 116,7
26
[ 151-50-8 ]
[ 63-74-1 ]
[ 3119-02-6 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 5, p. 2697 - 2706
[2] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 7, p. 1013 - 1015
27
[ 63-74-1 ]
[ 53297-68-0 ]
Yield
Reaction Conditions
Operation in experiment
95%
With N-chloro-succinimide In tetrahydrofuran at 40℃; for 25 h;
Under anhydrous and anaerobic conditions,Dissolve 1 mmol of sulfanilamide in 12 mL of tetrahydrofuran.Then add 2mmol NCS powder,The reaction was carried out at 40 °C for 25 h.The solvent was distilled off, the residue was extracted with 30 mL of ether, and the organic layer was washed with 5 mL of saturated potassium carbonate solution and 5 mL of saturated saline.The organic layer was dried over anhydrous sodium sulfate and subjected to column chromatography (dichloromethane:ethyl acetate 7:1).188 mg of pale yellow powder was obtained in a yield of 95percent.
Reference：
[1] Patent: CN107400060, 2017, A, . Location in patent: Paragraph 0011; 0029; 0030; 0036; 0037; 0043-0044; 0050-0051
[2] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1988, vol. 27, # 12, p. 1028 - 1030
28
[ 333-20-0 ]
[ 63-74-1 ]
[ 1718-39-4 ]
Reference：
[1] Revue Roumaine de Chimie, 1995, vol. 40, # 7-8, p. 643 - 652
[2] Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, vol. 32, # 1, p. 1071 - 1078
[3] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 11, p. 3916 - 3922
[4] Proceedings - Indian Academy of Sciences, Section A, 1940, # 12, p. 274,279
29
[ 63-74-1 ]
[ 1718-39-4 ]
Yield
Reaction Conditions
Operation in experiment
59%
With hydrogenchloride In water for 2 h; Heating / reflux
EXAMPLE 32 Preparation of Benzothiazole-6-sulfonyl Chloride; Part A Preparation of N-(4-Sulfonamidophenyl)thiourea A mixture of sulfanilamide (86 g, 0.5 mole), ammonium thiocyanate (76.0 g, 0.5 mole) and dilute hydrochloric acid (1.5 N, 1 L) was mechanically stirred and heated at reflux for 2 hr.. About 200 ML of water was distilled off and concentration of the reaction mixture afforded a solid.. The solid was filtered and was washed with cold water and air dried to afford 67.5 g (59percent) of the desired product as a white powder.
With calcium carbonate In dichloromethane; water at 0 - 20℃; Inert atmosphere
To a suspension of calcium carbonate (1.45 g, 14.5 mmol, Eq: 2.5) and thiophosgene (734 mg, 490 μ, 6.39 mmol, Eq: 1.1) in dichloromethane (13.2 g, 10 ml, 155 mmol, Eq: 26.8)/water (10.0 g, 10 ml, 555 mmol, Eq: 95.6) at 0, was added 4-aminobenzenesulfonamide (1 g, 5.81 mmol, Eq: 1.00). The reaction was gradually warmed to room temperature and stirred overnight. Added 15 mL IN HC1 slowly. Separated organic layer, and extracted the aqueous layer with ethyl acetate. Combined organic extracts were dried over sodium sulfate and concentrated to give 1.084 g (87percent) of desired product as a white solid.
87%
With hydrogenchloride In water at 20℃; for 0.5 h;
4-aminobenzenesulfonamide(17.20 g, 100 mmol)Dissolved in 200mL water,Add 50mL of concentrated hydrochloric acid and add at room temperatureSulfur phosgene(11.50 g, 100 mmol)Reaction for 30 minutes,Filtration gives 4-isothiocyanatobenzenesulfonamide,Washed with water to give the product 18.62g, yield 87percent
85%
With hydrogenchloride In water at 20℃; for 0.5 h;
4-amino-benzenesulfonamide Compound 2a (40 g, 240 mmol) in water (400 niL) in the presence of concentrated hydrochloric acid (100 mL) was reacted with thiophosgene (26.8 g, 240 mmol) at r.t. for 30 mins to provide 4-isothiocyanato- benzenesulfonamide Compound 2b
Reference：
[1] Patent: WO2014/6066, 2014, A1, . Location in patent: Paragraph 0211
[2] Patent: CN107253927, 2017, A, . Location in patent: Paragraph 0069; 0070; 0072
[3] Patent: WO2007/19191, 2007, A2, . Location in patent: Page/Page column 70
[4] Journal of the American Chemical Society, 1946, vol. 68, p. 2506
[5] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 12, p. 3475 - 3480
[6] European Journal of Medicinal Chemistry, 2009, vol. 44, # 10, p. 4148 - 4152
[7] Tetrahedron Letters, 2011, vol. 52, # 50, p. 6719 - 6722
[8] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 14, p. 3714 - 3718
36
[ 63-74-1 ]
[ 51908-29-3 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 6, p. 1873 - 1882
37
[ 63-74-1 ]
[ 39150-45-3 ]
Yield
Reaction Conditions
Operation in experiment
62%
at 20℃; for 5 h;
Sulfanilamide (0.43g, 0.0025mol) was stirred in 15mL of 6N halogen acid (0.08mol) at room temperature, and 2mL of 30percent hydrogen peroxide (0.02mol) was slowly added. After 5h, the product was filtered and recrystallized from ethanol. White solid. Yield: 62percent. 1H NMR (DMSO-d6, 400MHz): δ 7.79 (s, 2H, ArH), 7.26 (s, 2H, SO2NH2), 6.11 (s, 2H, NH2). 13C NMR (DMSO-d6, 100MHz): δ 145.8, 132.7, 129.5, 106.1.
Reference：
[1] Green Chemistry, 2011, vol. 13, # 8, p. 2187 - 2196
[2] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 229 - 236
[3] Analytical Chemistry, 1984, vol. 56, # 12, p. 2157 - 2160
[4] Organic Syntheses, 1955, vol. Coll. Vol. III, p. 262
[5] Gazzetta Chimica Italiana, 1948, vol. 78, p. 275,280
[6] Monatshefte fuer Chemie, 1915, vol. 36, p. 132
[7] Archiv der Pharmazie (Weinheim, Germany), 1943, vol. 281, p. 193,200
[8] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1989, vol. 28, # 6, p. 472 - 476
[9] Journal of Molecular Catalysis A: Chemical, 2014, vol. 390, p. 76 - 82
38
[ 7726-95-6 ]
[ 64-19-7 ]
[ 63-74-1 ]
[ 39150-45-3 ]
Reference：
[1] Monatshefte fuer Chemie, 1915, vol. 36, p. 132
39
[ 63-74-1 ]
[ 59772-49-5 ]
Reference：
[1] Patent: CN107400060, 2017, A,
40
[ 63-74-1 ]
[ 130-15-4 ]
[ 19992-50-8 ]
Reference：
[1] Chemische Berichte, 1944, vol. 77/79, p. 478,481
[2] Svensk Kemisk Tidskrift, 1942, vol. 54, p. 200,202
[3] Patent: WO2014/201016, 2014, A2, . Location in patent: Paragraph 00167; 00370
41
[ 64-17-5 ]
[ 63-74-1 ]
[ 130-15-4 ]
[ 19992-50-8 ]
Reference：
[1] Svensk Kemisk Tidskrift, 1942, vol. 54, p. 200,202
42
[ 60-12-8 ]
[ 63-74-1 ]
[ 587850-67-7 ]
Yield
Reaction Conditions
Operation in experiment
80%
at 120℃; for 12 h; Inert atmosphere; Schlenk technique
Under nitrogen protection,A mixture of 4-aminobenzenesulfonamide (172 mg, 1 mmol)[Cp * IrCl2] 2 (8 mg, 0.01 mmol, 1 molpercent),Potassium hydroxide (56 mg, 1 mmol),Phenethyl alcohol (610mg, 5equiv) were added sequentially to the reaction flask 25mLSchlenk.The mixture was allowed to react at 120 ° C for 12 hours,Cooled to room temperature,The solvent was removed under vacuum.And then subjected to column chromatography (developing solvent:Ethyl acetate / n-hexane) to give the pure title compound,Yield: 80percent.
Reference：
[1] Organic Letters, 2015, vol. 17, # 10, p. 2350 - 2353
[2] Patent: CN106146362, 2016, A, . Location in patent: Paragraph 0022; 0023; 0024; 0025; 0026; 0027; 0028-0035
43
[ 63-74-1 ]
[ 17852-52-7 ]
Yield
Reaction Conditions
Operation in experiment
55%
Stage #1: With hydrogenchloride; sodium nitrite In water at 0 - 4℃; for 0.5 h; Stage #2: at 0℃; for 4 h;
Compound 30c, 3-[1-{p-(Sulfonamido)phenyl}-5-p-tolyl-1H-pyrazol-3-yl]propanoic acid., was synthesized by the method depicted in FIG. 2. Briefly, 4'-methylacetophenone and succinnic hydride were reacted in the presence of lithium diisopropanolamine (LDA) and tetrahydrofuran (THF) for 1 hour at -78° C. to produce p-tolyl-4,6-dioxohexanoic acid as a white solid (66percent yield). Also sulfanilamide has reacted with sodium nitrite (NaNO2) and concentrated hydrochloric acid at 0-4° C. for 30 minutes, after which tin(II) chloride (SnCl2) was added and the reaction allowed to continue for an additional 4 hours at 0° C. to produce 4-sulfonamidophenylhydrazine hydrochloride as a pale yellow solid (55percent yield). The 4,6,dioxo-6-p-tolylhexanoic acid and the 4-sulfonamidophenylhydrazine hydrochloride were then complexed for 16 hours at room temperature in the presence of triethanolamine (TEA) in methanol to produce Compound 30c as a yellow solid (76percent yield).
Reference：
[1] Journal of Medicinal Chemistry, 2007, vol. 50, # 18, p. 4444 - 4452
[2] Organic Letters, 2012, vol. 14, # 19, p. 5030 - 5033,4
[3] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 4, p. 913 - 922
[4] Patent: US2007/292352, 2007, A1, . Location in patent: Page/Page column 45-46
[5] Patent: US2003/236294, 2003, A1, . Location in patent: Page 9
[6] Patent: US2003/109709, 2003, A1,
[7] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 9, p. 2997 - 3004
[8] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3295 - 3300
[9] Research on Chemical Intermediates, 2017, vol. 43, # 1, p. 271 - 281
With cerium(III) chloride heptahydrate; In ethanol; water; at 75.0℃; for 72.0h;
General procedure: Cerium chloride heptahydrate (36 mg; 97 muetaiotaomicron), followed by 4- aminobenzenesulfonamide (689 mg; 4.00 mmol), was added to a suspension of naphthalene- 1 ,4- dione (316 mg; 2.00 mmol) in 95% ethanol (8.0 mL). The reaction vial was capped then put intoa 75 C block. After three days the reaction was cooled to room temperature, then 80 mL of 1.0 M citric acid was added with vigorous stirring. The insoluble material was collected by filtration, washed with water, and dried in vacuo at 45 C affording crude product as a rust colored solid (370 mg). A portion of this (225 mg) was purified by pRPLC yielding 4-((l ,4-dioxo-l ,4- dihydronaphthalen-2-yl)amino)benzenesulfonamide as a rust-colored solid (101 mg). LH NMR (400 MHz, DMSO-i delta 9.45 (s, 1H), 8.09 (dd, J = 1.0, 7.6 Hz, 1H), 7.98 (dd, J = 1.1 , 7.6 Hz, 1H), 7.92 - 7.79 (m, 4H), 7.60 (m, 2H), 7.37 (s, 2H), 6.33 (s, 1H). 13C NMR (125 MHz, DMSO- d6) delta 183.0, 181.3, 145.2, 141.5, 139.6, 134.9, 132.9, 132.3, 130.4, 127.0, 126.2, 125.3, 122.7, 103.8. LC-MS (ESI+): Purity at 214 nm is 100%. HRMS: 329.0591 (calcd for C16H13N204S = [M+H ); 329.0594 (found / [M+H]+)
With hydrogen bromide; dihydrogen peroxide; at 20℃; for 5.0h;
Sulfanilamide (0.43g, 0.0025mol) was stirred in 15mL of 6N halogen acid (0.08mol) at room temperature, and 2mL of 30% hydrogen peroxide (0.02mol) was slowly added. After 5h, the product was filtered and recrystallized from ethanol. White solid. Yield: 62%. 1H NMR (DMSO-d6, 400MHz): delta 7.79 (s, 2H, ArH), 7.26 (s, 2H, SO2NH2), 6.11 (s, 2H, NH2). 13C NMR (DMSO-d6, 100MHz): delta 145.8, 132.7, 129.5, 106.1.
With sodium perborate; hydrogen bromide; at 80 - 90℃;
To a mixture of 50.0 g sulfanilamide, 850 mL water and 200 mL 48% HBr solution, 90.0 g sodium perborate was added at 85 C. The mixture was stirred at 80-85 C for 30 min and then was cooled to room temperature and filtered. The residue was washed to be neutral by water. The solid was desulfonated by reacting with 70% sulfuric acid solution for 3 h under reflux. Crude product was obtained by steam distillation and further purified by recrystallization in ethanol. 1H NMR (500 MHz, CDCl3, delta in ppm): 7.35-7.40 (d, 2H, Ar-Hm), 6.5 (t, 1H, Ar-Hp).
With N-chloro-succinimide; In tetrahydrofuran; at 40℃; for 25h;
Under anhydrous and anaerobic conditions,Dissolve 1 mmol of sulfanilamide in 12 mL of tetrahydrofuran.Then add 2mmol NCS powder,The reaction was carried out at 40 C for 25 h.The solvent was distilled off, the residue was extracted with 30 mL of ether, and the organic layer was washed with 5 mL of saturated potassium carbonate solution and 5 mL of saturated saline.The organic layer was dried over anhydrous sodium sulfate and subjected to column chromatography (dichloromethane:ethyl acetate 7:1).188 mg of pale yellow powder was obtained in a yield of 95%.
2-[4-chloro-3-(3-chloro-5-cyano-phenoxy)-phenyl]-N-(4-sulfamoyl-phenyl)-acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With LiOH; sodium hydrogencarbonate; potassium carbonate; In ethanol; water; N,N-dimethyl-formamide; acetone;
step 6-A solution of 40 (1.07 g, 5 mmol), <strong>[6575-00-4]3,5-dichloro-benzonitrile</strong> (1.3 g, 7.56 mmol), K2CO3 (2.07 g, 15.0 mmol) and NMP (10 mL) was stirred and heated to 110 ° C. for 6 h. The reaction mixture was cooled to RT and diluted with H2O (50 mL) and twice extracted with EtOAc. The combined organic extracts were washed sequentially with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluding with EtOAc/hexane (10:90) to afford 0.328 g of 102a. step 7-To a solution of 102a (0.80 g; 0.1.98 mmol) and LiOH (142.5 mg, 5.94 mmol) dissolved in EtOH (8 mL) and water (2 mL) and stirred for at RT. The mixture was concentrated in vacuo and the residue acidified with 1 N HCl and twice extracted with EtOAc. The combined extracts were washed sequentially with water and brine, dried (Na2SO4), filtered and evaporated to afford 102b which was used without further purification in step 8. Step 8-To a solution of 102b (0.75 g, 1.994 mmol) and DCM (8 mL) was added DMF (2 drops) and 0.05 mL of and oxalyl chloride (0.348 mL, 0.505 g; 3.99 mmol). The reaction mixture was stirred overnight at RT. The volatile reactants were removed in vacuo and the crude acid chloride 102c was used directly in the next step. Step 9-The acid chloride 102c (0.092 g)was dissolved in 3 mL of acetone and purged with nitrogen. A separate flask was charged with 4-amino-benzenesulfonamide (0.046 g; 0.270 mmol) and water (1 mL) was added to dissolve the sulfonamide. NaHCO3 (0.050 g) was added and the acetone solution slowly added and allowed to stir overnight. The reaction mixture was extracted with EtOAc and washed with 10percent HCl and brine. The EtOAc solution was dried (Na2SO4), filtered and evaporated and the crude product purified by SiO2 chromatography eluding with EtOAc:hexanes (60:40) to afford I-1: mp 211-213; ms=476. Compound I-3 was prepared in a by a similar procedure except in step 9, 4-amino-benzene was replaced by 3-(4-amino-3-methyl-phenoxy)-propane-1-sulfonic acid amide (J. H. Chan et al. J. Med. Chem. 2004 47(5):1175-1182)
2-[3-(3-Bromo-2,5-dichloro-phenoxy)-4-ethyl-phenyl]-N-(4-sulfamoyl-phenyl)-acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; sodium hydrogencarbonate; potassium carbonate; In water; ethyl acetate; acetone;
EXAMPLE 21 2-[3-(3-Bromo-2,5-dichloro-phenoxy)4-ethyl-phenyl]-N-(4-sulfamoyl-phenyl)-acetamide (I-35) step 1-To a solution of 12a (0.450 g; 2.160 mmol) and NMP (5 mL) was added K2CO3 (0.896 g; 6.48 mmol) and <strong>[202865-57-4]1-bromo-2,5-dichloro-3-fluoro-benzene</strong> (0.580 g; 2.38 mmol). The reaction was heated to 120 C. and monitored by TLC. After 8 h the reaction was cooled to RT and 10% HCl was added. The mixture was extracted with EtOAc and the combined extracts were washed with H2O and brine. The extracts were dried (Na2SO4), filtered and evaporated. The crude product was purified by SiO2 chromatography eluding with a gradient of hexane/EtOAc (100:0 to 60:40) to afford 146. steps 2 and 3-Hydrolysis and formation of the acid chloride were carried as described in step 7and 8 of Example 1 and used without additional purification. step 4-The acid chloride from step 3 (0.112 mmol) was dissolved in acetone (1 mL) and the flask was purged with nitrogen. NaHCO3 (0.019 g; 0.224 mmol) was added followed by 4-amino-benzenesulfonamide (0.019 g; 0.112 mmol) and water (2 mL). The mixture was sonicated for 5 min and allowed to stir for 12 h at RT. The reaction mixture was filtered and the crude product was washed sequentially with water and diethyl ether to afford I-35. Compound I-36 was prepared in the same manner except 4-amino-benzenesulfonamide was replaced with 4-amino-3-methyl-benzenesulfonamide. Compound I-37 was prepared in the same manner except 4-amino-benzenesulfonamide was replaced with 2-chloro-phenylamine.
With methanesulfonic acid; sodium hydrogencarbonate; In methanol; ethanol; water; N,N-dimethyl-formamide;
Example 3A 4-[(2-Oxo-1,2-dihydro-3H-pyrrolo[2,3-b]pyridin-3-ylidene)methyl]amino}benzenesulfonamide Dimethylformamide di-tert-butyl acetal (180 mg, 0.89 mmol) was added to a solution of 1,2-dihydro-3H-pyrrolo[2,3-b]pyridin-2-one (70 mg, 0.52 mmol) in 0.25 ml DMF, and the reaction mixture was slowly warmed to 100 C. The cooled solution was then diluted with 5 ml of ethanol. Sulfanilamide (172 mg, 1.00 mmol) and methanesulfonic acid (60 mg, 0.63 mmol) were added, and the reaction mixture was stirred at reflux for 2 hours. The cooled solution was diluted with 4 ml of water, treated with NaHCO3 (70 mg, 0.83 mmol) and stirred 10 min. The resulting solid was filtered, washed with water and ethanol, and then suspended in boiling methanol and filtered upon cooling. Inorganics were removed by filtration through a short silica gel column, eluding with DMF. The resulting solution was diluted with an equal volume of ice water, and the suspension was refrigerated overnight. The solid was isolated by filtration and dried to give 36 mg (21%) of the title compound as a yellow solid: 1H NMR (400 MHz, DMSO-d6) (4:1 ratio of Z:E isomers): delta (Z) 11.07 (s, 1H), 10.76 (d, J=12.4 Hz, 1H), 8.67 (d, J=12.5 Hz, 1H), 7.92 (d, J=5.1 Hz, 1H), 7.84 (d, J=7.3 Hz,
36 mg (21%)
With methanesulfonic acid; sodium hydrogencarbonate; In methanol; ethanol; water; N,N-dimethyl-formamide;
EXAMPLE 3 4-[(2-oxo-1,2-Dihydro-3H-pyrrolo[2,3-b]pyridin-3-ylidene)methyl]amino}benzenesulfonamide Dimethylformamide di-tert-butyl acetal (180 mg, 0.89 mmol) was added to a solution of 1,2-dihydro-3H-pyrrolo[2,3-b]pyridin-2-one (70 mg, 0.52 mmol) in 0.25 ml DMF, and the reaction mixture was slowly warmed to 100 C. The cooled solution was then diluted with 5 ml of ethanol. Sulfanilamide (172 mg, 1.00 mmol) and methanesulfonic acid (60 mg, 0.63 mmol) were added, and the reaction mixture was stirred at reflux for 2 h. The cooled solution was diluted with 4 ml of water, treated with NaHCO3 (70 mg, 0.83 mmol) and stirred 10 min. The resulting solid was filtered, washed with water and ethanol, and then suspended in boiling methanol and filtered upon cooling. Inorganics were removed by filtration through a short silica gel column, eluding with DMF. The resulting solution was diluted with an equal volume of ice water, and the suspension was refrigerated overnight. The solid was isolated by filtration and dried to give 36 mg (21%) of the title compound as a yellow solid: 1H NMR (400 MHz, DMSO-d6) (4:1 ratio of Z:E isomers): delta (Z) 11.07 (s, 1H), 10.76 (d, J=12.4 Hz, 1H), 8.67 (d, J=12.5 Hz, 1H), 7.92 (d, J=5.1 Hz, 1H), 7.84 (d, J=7.3 Hz, 1H), 7.77 (d, J=8.7 Hz, 2H), 7.55 (d, J=8.6 Hz, 2H), 7.25 (s, 2H), 6.93 (dd, J=7.3, 5.1 Hz, 1H); (E) 10.79 (s, 1H), 9.70 (d, J=13.4 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H). ESI-MS m/z 315 (M-H). Anal. Calcd. for C14H12N4O3S. 0.5 H2O: C, 51.68; H, 4.03; N, 17.03. Found: C, 51.75; H, 3.95; N, 17.26.
N-(3-chloro-4-methoxybenzylidene)-4-sulfamoylaniline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
79(i) N-(3-Chloro-4-methoxybenzylidene)-4-sulfamoylaniline Following a procedure similar to that described in Example 1(i), but using <strong>[4903-09-7]3-chloro-4-methoxybenzaldehyde</strong> and 4-sulfamoylaniline as starting materials, the title compound was obtained as a pale yellow powder (yield 72percent). Nuclear Magnetic Resonance Spectrum (270 MHz, hexadeuterated dimethyl sulfoxide) delta ppm: 8.37 (1H, singlet); 8.00 (1H, doublet, J=2 Hz); 7.93 (2H, doublet, J=9 Hz); 7.77 (1H, doublet of doublets, J=2 and 9 Hz); 7.24 (2H, doublet, J=9 Hz); 7.09 (1H, doublet, J=9 Hz); 6.90 (2H, broad doublet, J=5 Hz); 3.99 (3H, singlet).
4-(6-bromoquinazolin-2-ylamino)benzenesulfonamide hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In isopropyl alcohol; at 90℃; for 14.0h;
Step 5: 4-(6-Bromoquinazolin-2-ylamino)benzenesulfonamide; To a 0.50 M solution of <strong>[882672-05-1]6-bromo-2-chloroquinazoline</strong> in 2-propanol was added sulfanilamide (1.0 eq). The reaction was stirred at 90 C. for 14 h. The hydrochloride was collected by vacuum filtration and used without further purification. Alternatively, the crude reaction mixture was concentrated, purified by reverse-phase HPLC, and lyophilized to give the desired compound as its trifluoroacetic acid salt. ES/MS m/z 379, 381 (MH+).
General procedure for synthesis of the target molecules: Aromatic aldehyde (2 mmol) and aromatic amine were added to the mixed solvent of anhydrous ethanol-chloroform (5-10 mL, v/v = 3:1). This mixture was stirred vigorously until the appearance of the precipitate, and then ketone (2 mmol) was added followed by a few droplets (0.1-0.2 mL) of concentrated hydrochloric acid as catalyst. Stirred continuously at 20-32 C, and if necessary, additional amount of anhydrous ethanol was added. The reaction progress was monitored by TLC. Upon completion, the suspension was cooled in the refrigerator for about 2-5 h. The solid was subsequently collected by filtration. The filter cake was dispersed in 95% ethanol (4-10 mL), adjusting to pH 7-8 with 10% K2CO3 and stirring for approximately 2 h. Subsequently, the suspension was filtered with suction on a sintered glass funnel, the filter cake obtained was washed thoroughly with water (2 × 5 mL) and cool absolute ethanol (2 × 1.5 mL), and then dried in vacuo overnight to afforded the crude product. Recrystallising from ethanol, methanol, chloroform, or ethanol-acetone affords analytically pure product. Melting point was determined, and the structure was confirmed by 1H NMR, 13C NMR, ESI MS and HRMS techniques
General procedure for synthesis of the target molecules: Aromatic aldehyde (2 mmol) and aromatic amine were added to the mixed solvent of anhydrous ethanol-chloroform (5-10 mL, v/v = 3:1). This mixture was stirred vigorously until the appearance of the precipitate, and then ketone (2 mmol) was added followed by a few droplets (0.1-0.2 mL) of concentrated hydrochloric acid as catalyst. Stirred continuously at 20-32 C, and if necessary, additional amount of anhydrous ethanol was added. The reaction progress was monitored by TLC. Upon completion, the suspension was cooled in the refrigerator for about 2-5 h. The solid was subsequently collected by filtration. The filter cake was dispersed in 95% ethanol (4-10 mL), adjusting to pH 7-8 with 10% K2CO3 and stirring for approximately 2 h. Subsequently, the suspension was filtered with suction on a sintered glass funnel, the filter cake obtained was washed thoroughly with water (2 × 5 mL) and cool absolute ethanol (2 × 1.5 mL), and then dried in vacuo overnight to afforded the crude product. Recrystallising from ethanol, methanol, chloroform, or ethanol-acetone affords analytically pure product. Melting point was determined, and the structure was confirmed by 1H NMR, 13C NMR, ESI MS and HRMS techniques
With hydrogenchloride; copper(ll) sulfate pentahydrate; sodium nitrite; In water; at 0 - 80℃;
A cold solution of NaNO2 (1.2 g, 17 mmol) was added to a suspension of sulfanilamide (2.5 g, 15 mmol) in 20 mL of a 2.3 N HCl solution at 0 C with vigorous stirring. The resultant solution was poured into a suspension of KCN (4.16 g, 64 mmol) and CuSO4·5H2O (3.85 g, 15 mmol) in 20 mL of water. After stirring for 30 min, the solution was heated to 80 C and then chilled. The precipitate was filtered, dried and extracted with 5% ethanol in benzene Soxhelt apparatus. The organic extract was concentrated and the solid recrystallized from water to afford p-cyanobenzenosulfonamide (1.6 g, 60%). m.p. 173.2 C determined by thermogravimetry measures (TG-DT) and by melting point.
Dissolved 0.500 g <strong>[17823-69-7]2-cyano-3,3-bis(methylthio)acrylamide</strong> in 15 mL EtOH and added Sulfanilamide (1.0 eq.) . Stirred reaction at 75 C until starting amide was absent by HPLC. Once complete (18 hrs), reaction was brought to room temperature and filtered to obtain a light yellow powder as product. Product was allowed to dry under vacuum for 1 hr. Product was then suspended in 10 mL EtOH and hydrazine hydrate (1 eq.) was added dropwise. Reaction was heated at 75 C until intermediate was absent (HPLC). Once intermediate was absent (18 hrs), reaction was brought to room temperature and filtered to obtain 5-amino-3-((4-sulfamoylphenyl)amino)-lH-pyrazole-4-carboxamide as a yellow powder. Product was allowed to dry under vacuum for 1 hr. 5-amino-3-((4-sulfamoylphenyl)amino)-lH-pyrazole-4-carboxamide
4-[(benzo[b]thiophen-3-ylmethylene)amino]benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
25%
In methanol; at 70℃; for 24h;
General procedure: Sulfanilamide (1.0 equiv) was dissolved in dry MeOH and theappropriate aldehyde (1.0 equiv) was added to the reaction. Thesolution was stirred until the formation of a precipitate was completedwhich was collected by filtration, washed with ice-coldMeOH and dried under vacuo to afford the desired compounds 1-17.
In methanol;
General procedure: The preparation of compounds 1-17 investigated in this studywas carried out according to the procedure described by Supuranet al. (1996).26 Sulfonilamide/3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide (1.0 equiv) was dissolved in dryMeOH and stoichiometrical amount of the appropriatearomatic/herocyclic aldehydes containing either hydrophobic orhydrophilic moieties was added to the reaction. The solution wasstirred until the formation of a precipitate was completed whichwas collected by filtration, washed with ice cold MeOH and driedunder vacuo to afford the desired compounds 1-17.The synthesis and the full characterization of all compounds1-17 investigated here as CA inhibitors are reported elsewhere.
cis-cis-4-(2,3-dimethylphenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With indium(III) chloride;
General procedure: Nineteen compounds were synthesizedthat differed only in the pattern of methyl substitution of an aromatic substituent located at position 2 of a tetrahydroisoquinoline ring (see Fig. 1). Compounds were prepared by InCl3-catalyzed reaction of sulfanilamide, cyclopentadiene, and the corresponding substituted benzaldehyde, according to methods described previously (27).
4-amino-N-(cyclohexylmethyl)benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; caesium carbonate; In tert-Amyl alcohol; at 120℃; for 12h;Inert atmosphere; Schlenk technique;
Under nitrogen, 4-aminobenzenesulfonamide (172 mg, 1 mmol), [Cp * IrCl2] 2 (8 mg, 0.01 mmol,1 mol%), cesium carbonate (130 mg, 0.4 mmol), cyclohexylmethanol (228 mg, 2 mmol), t-amyl alcohol (1.0ML) were sequentially added to a 25 mL Schlenk reaction flask. The mixture was allowed to react at 120 C for 12 hours and then cooledThe solvent was removed under vacuum at room temperature. And then purified by column chromatography (developing solvent: ethyl acetate / n-hexane)The target compound was 83% yield.
General procedure: Sulfanilamide 1 (5 mmol) was refluxed with appropriate amines (5 mmol) in ethanol. After completion of the reaction (monitored by TLC), the mixture was reduced in vacuo, and the resulting solution was allowed to stand until solid product crystallized from solution. The resulting imines 2a-n was recrystallized from ethanol in 85-95% yield.
With potassium carbonate; In dichloromethane; at 40℃; for 8h;
sulfanilamide (8.6 g, 0.05 mol)Potassium carbonate (6.8 g, 0.05 mol) in dichloromethane solution of intermediate III,Was loaded into a 150 ml three-neck reaction flask,The reaction was stirred at 40 C for 8 hours,A solution of the sulfonamine truncated dengurin derivative in dichloromethane.A solution of the sulfonamide truncated pendant dicarboxylate in methylene chloride,Washed with 0.1 M NaOH solution,Collecting organic layer,The organic layer was washed with 0.1 M HCl solution,Collecting water,Adjust the PH value to neutral,The organic layer was extracted with dichloromethane,Vacuum drying of dichloromethane,Sulfonated truncated pterosin derivatives3.2 g (yield 11.7%).
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; at 20℃;
Protected-GP (17, 10 mmol) and HOBt (10 mmol) in dichloromethane (DCM) was stirred andcooled in ice bath at 0C. Sulfanilamide (6, 10 mmol) triethylamine (10 mmol) and EDC (10mmol) were added. The mixture was allowed to warm to room temperature and stirringcontinued overnight. The mixture was diluted with CHCI3 and washed with 1N HC1(thoroughly), aq. sat. NaHCO3 and NaCl solution. The organic phase was dried MgSO4 andevaporated. The crude residues were purified by column chromatography using n-hexane/ ethylacetate resulted in 18 in 82% yield.
4-(5-chlorophthalimido)benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
In N,N-dimethyl-formamide;Reflux; Alkaline conditions;
General procedure: A mixture of anhydrides 1a,b (1 mmol) and the appropriate benzensulfonamides (1 mmol) namely, 4-aminobenzenesulfonamide 2a, 4-(aminomethyl)benzenesulfonamide 2b and 4-(2-aminoethyl)benzenesulfonamide 2c in DMF (10 ml) was heated under reflux for 3-5 h. Then, the reaction mixture was poured on ice cold water. The separated solid was collected by filtration, dried and crystallized from ethanol to afford the target compounds 3a-f, respectively. 4.1.1.1. 4-(5-Chlorophthalimido)benzenesulfonamide 3d..4.1.1.1. 4-(5-Chlorophthalimido)benzenesulfonamide 3d. White powder(yield 63%); m.p. 176-178 C; IR (KBr, upsilon cm-1): 3347, 3253 (NH2),3114 (CeH aromatic), 2945 (CeH aliphatic), 1709 (C]O), 1329, 1151(SO2);1H NMR (DMSO-d6, 600 MHz) delta (ppm): 7.54 (s, 2H, NH2, D2Oexchangeable), 7.63-7.65 (d, 2H, Ar-H), 7.90-7.92 (d, 2H, Ar-H),7.94-7.97 (m, 3H, Ar-H).; Anal. Calcd. for C14H9ClN2O4S (336.00): C,49.93; H, 2.69; N, 8.32; Found: C, 49.55; H, 2.27; N, 8.02.
2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(4-sulfamoylphenyl)acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
36%
General procedure: EDCI (2.0 eq) was added to a solution of 1-carboxymethyl 5-fluorouracil 2 (0.2 g, 1.0 eq), HOBt (0.5 eq) and DMAP (0.03 eq) indry DMF (2 ml) under a nitrogen atmosphere and the reactionmixture was stirred at r.t. until the consumption of the startingmaterial (TLC monitoring). Thereafter the proper aminobenzenesulfonamide3a-3e (1.1 eq) was added to the reactionmixture, that was stirred at r.t. until the disappearance of theactivated ester was observed (TLC monitoring) and then quenchedwith ice and HCl(aq) 2M. The formed precipitate was filtered undervacuo and recrystallized from the minimum amount of water toafford the titled compounds as white powders.4.1.2.1. 2-(5-Fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(4-sulfamoylphenyl)acetamide 4a. Compound 4a was obtained accordingthe general procedure earlier reported using 1-carboxymethyl 5-fluorouracil 2 (0.2 g, 1.0 eq), HOBt (0.5 eq),DMAP (0.03 eq) and 4-aminobenzenesulfonamide 3a (1.1 eq) in dryDMF (2 ml). 36% yield; m.p. >300 C; silica gel TLC Rf 0.50 (MeOH/CH2Cl2 10% v/v); dH (400 MHz, DMSO-d6): 11.98 (s, 1H, exchangewith D2O, CONHCO), 10.67 (s, 1H, exchange with D2O, CONH), 8.14(d, J 6.7 Hz, 1H, AreH), 7.82 (d, J 8.7 Hz, 2H, AreH), 7.76 (d,J 8.8 Hz, 2H, AreH), 7.31 (s, 2H, exchange with D2O, SO2NH2), 4.57(s, 2H, CH2); dC (100 MHz, DMSO-d6): 166.89, 158.46 (d, J2CF 25.7 Hz), 150.74, 142.26, 140.21 (d, J2 CF 228.6 Hz). 139.70,131.97 (d, J2 CF 34.0 Hz), 127.78, 119.70, 51.22; dF (376 MHz,DMSO-d6): 170.40 (d, J 5.7 Hz); m/z (ESI negative) calcd forC12H10FN4O5S [M H]- 341.0, found 341.1.
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