* 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.
With ammonium hydroxide; In methanol; at 20℃; for 5h;
General procedure: Standard Procedure D for the Preparation of Sulfonamides (0054) A solution of sulfonyl chloride in methanol and ammonium hydroxide solution was stirred at 0 C. or room temperature. After the reaction was complete, methanol was removed under reduced pressure. The solution was extracted with ethyl acetate. The combined organic layers were dried over MgSO4(s), filtered, and concentrated to give the desired products without further purification. Step 1. 2,4,6-Trimethylbenzenesulfonamide Following standard procedure D, 2-mesitylenesulfonyl chloride (0.890 g, 4.07 mmol), methanol (8.0 mL), and ammonium hydroxide solution (20 mL) were used to carry out the reaction. After the reaction was stirred at room temperature for 5 h and work-up, 2,4,6-trimethylbenzenesulfonamide (0.241 g, 30%) was obtained as a beige solid. 1H NMR (CDCl3, 400 MHz) delta 6.96 (s, 2H), 4.81 (br s, 2H), 2.65 (s, 6H), 2.30 (s, 3H).
4
[ 50-84-0 ]
[ 1524-40-9 ]
2,4-dichloro-N-(3-fluorophenylsulfonyl)benzamide[ No CAS ]
With hydrogenchloride; sodium hydroxide; dimethyl amine; In water; dimethyl sulfoxide;
EXAMPLE 4 Preparation of N-[[(4-chlorophenyl)amino]carbonyl]-3-(dimethylamino)benzenesulfonamide To a solution of <strong>[1524-40-9]3-fluorobenzenesulfonamide</strong> (3.0 g, 17.1 mmoles) in 15 ml of dimethyl sulfoxide was added 29 ml of dimethylamine (40% w/w in water). This mixture was sealed in a pressure tube and heated to 138 C. for 16 hours. The reaction mixture was allowed to cool to room temperature, and then added to 500 ml of water. The mixture was extracted with ethyl acetate (1*400 ml, 1*100 ml). The combined organic layers were washed with 300 ml of 1N hydrochloric acid. The acid wash was neutralized with 300 ml of 1N sodium hydroxide and extracted with ethyl acetate (300 ml). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to yield 1.83 g (9.1 mmoles, 53%) of 3-(dimethylamino)benzenesulfonamide as a white solid.
N-(3-chloroquinoxalin-2-yl)-3-fluoro-benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
<strong>[1524-40-9]3-fluorobenzenesulfonamide</strong> (250 mg, 1.4 mmol), 2, 3-dichloroquinoxaline (284.1 mg, 1.4 mmol) and dry K2CO3 (198.4 mg, 1.4 mmol) are dissolved in dry DMF (0.8 ml) and heated up to 1350C in a sealed tube for 2.5 h. When TLC confirms the completion of the reaction, the reaction mixture is cooled down to rt and quenched by addition of water (4 ml) and AcOH (0.03 ml). The residue obtained is triturated and the resulting solid is filtered and washed with water until neutral pH then dried under vacuum to afford 400 mg (83 %) of the title compound as an off white solid. IH NMR (DMSO-d6) delta 12.8-10.9 (br s, IH), 8.05-7.62 (m, 7H), 7.54 (td, J = 2.0, 8.5 Hz, IH). HPLC (max plot) 94%; Rt 3.79 min. LC/MS: (ES+): 338.1, (ES-): 336.1.
2',3'-o-isopropylideneadenosine-5-carboxylic acid[ No CAS ]
C19H19FN6O6S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 30h;Inert atmosphere; Automated synthesizer;
General procedure: A mixture of 2 (1 mmol), DCC (1.2 mmol), DMAP (1 mmol) and the appropriate sulfonamide (2 mmol) in methylene chloride was allowed to shake under an argon atmosphere at room temperature for 30 h. After solvent removal, the obtained crude material was dissolved in methanol pre-adsorbed on silica gel and purified using the automated flash chromatography system. The pure intermediate was hydrolyzed following the same protocol used for the preparation of compounds 3-49.
1-methyl-4-((3-methoxyphenyl)amino)-7-chloro-1H-indole-2-carboxylic acid[ No CAS ]
1-methyl-4-((3-methoxyphenyl)amino)-7-chloro-N-(3-fluorophenylsulfonyl)-1H-indole-2-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
56.2%
With dmap; triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20℃;Inert atmosphere;
Ar under the protection, A solution of 1-methyl_4 - ((3-methoxyphenyl) amino) -7-chloro-111-indole-2-carboxylic acid (1001 ^ 0 · 30mmo 1) Dissolved in dry DCM, Followed by addition of HATU (172 mg, 0.45 mmo 1) DMAP (18 mg, 0.15 mmo 1) And TEA (92 mg, 0.90 mmol), After stirring, add <strong>[1524-40-9]3-fluorobenzenesulfonamide</strong> (79 mg, 0.45 mmol), overnight at room temperature, In addition to the solvent, washed with hydrochloric acid, washed with water, combined with EA layer, column separation of light yellow green solid (82mg, 56.2%)
2-chloro-6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]pyridine-3-carboxylic acid[ No CAS ]
2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]pyridine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
259 mg
To 2-chloro-6-[3-[2-[l-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-l-yl]pyridine-3-carboxylic acid (0.200 g, 0.532 mmol) in THF (1.7 mL) was added 1,1 '-carbonyldiimidazole (108.8 mg, 0.6707 mmol) and reaction was stirred for 1 hour. 3-Fluorobenzenesulfonamide (93.25 mg, 0.5323 mmol) was added, followed by 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) (267.5 mg, 262.8 mu,, 1.757 mmol) and reaction was stirred for 2 hours. The reaction was diluted with ethyl acetate and 1 M aqueous citric acid and layers were separated. The organics were dried and concentrated and resulting solid 2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[2-[l-(trifluoromethyl)cyclopropyl]emoxy]pyrazol4-yl]pyridine-3-carboxamide (approximately 259 mg) was used in the next step without characterization.
2-chloro-6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]pyridine-3-carboxylic acid[ No CAS ]
N-(3-fluorophenyl)sulfonyl-6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide[ No CAS ]
2-chloro-6-[3-(1-trifluoromethylcyclobutylmethoxy)pyrazole-1-yl]nicotinic acid[ No CAS ]
2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[[1-(trifluoromethyl)cyclobutyl]methoxy]pyrazol-1-yl]pyridine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
99%
2-Chloro-6-[3-[[l-(tri£luoromethyl)cyclobutyl]methoxy]pyrazol-l-yl]pyridine-3-carboxylic acid (150 mg, 0.3992 mmol) and carbonyl diimidazole (approximately 81.69 mg, 0.5038 mmol) were combined in THF (1.339 mL) and stirred for 2 h. At this point, <strong>[1524-40-9]3-fluorobenzenesulfonamide</strong> (approximately 69.93 mg, 0.3992 mmol) was added followed by DBU (approximately 202.6 mg, 199.0 mu,, 1.331 mmol) and the reaction was stirred for an additional 2h at room temperature. The reaction was diluted with ethyl acetate and washed with a 1M citric acid solution, followed by brine. The organics were separated, dried over sodium sulfate, and evaporated to give 2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[[l- (trifluoromethyl)cyclobu?yl]methoxy]pyrazol-l-yl]pyridine-3-carboxamide (210 mg, 99%) ESI-MS m/z calc. 532.0595, found 533.0 (M+1) +; Retention time: 0.77 minutes.
2-chloro-6-[3-(1-trifluoromethylcyclobutylmethoxy)pyrazole-1-yl]nicotinic acid[ No CAS ]
N-(3-fluorophenyl)sulfonyl-6-[3-[[1-(trifluoromethyl)cyclobutyl]methoxy]pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide[ No CAS ]
2-chloro-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]pyridine-3-carboxylic acid[ No CAS ]
chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]pyridine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
2-chloro-6-[3-[[l-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-l-yl]pyridine-3-carboxylic acid (181 mg, 0.5 mmol) and carbonyldiimidazole (97 mg. 0.6 mmol) were combined in THF (2.5 mL) and stirred at room temperature for 30 minutes. 3-iluorobenzenesulfonamide (114 mg, 0.65 mmol) was added, followed by DBU (0.09 mL, 0.6 mmol) and the reaction mixture was stirred for 3 h at room temperature. The reaction mixture was diluted with 10 mL ethyl acetate, and washed with 10 mL 1M aqueous citric acid. The organics were dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a 0-8% gradient of methanol in dichloromethane to give 2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[[l-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-l-yl]pyridine-3-carboxamide (190 mg, 73%) ESI-MS m/z calc. 518.0439, found 519.1 (M+l)+; Retention time: 0.72 minutes.
2-chloro-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]pyridine-3-carboxylic acid[ No CAS ]
N-(3-fluorophenyl)sulfonyl-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide[ No CAS ]
2-chloro-6-[3-[(2,2,3,3-tetramethylcyclopropyl)methoxy]pyrazol-1-yl]pyridine-3-carboxylic acid[ No CAS ]
2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[(2,2,3,3-tetramethylcyclopropyl)methoxy]pyrazol-1-yl]pyridine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
2-Chloro-6-[3-[(2,2,3,3-tetramethylcyclopropyl)methoxy]pyrazol-l-yl]pyridine-3-carboxylic acid (150 mg, 0.429 mmol) was dissolved/suspended in THF (2 mL), and carbonyl diimidazole (64.2 mg, 0.396 mmol) was added. The suspension was allowed to stir at room temperature for 1.5 hours. <strong>[1524-40-9]3-fluorobenzenesulfonamide</strong> (75.1 mg, 0.429 mmol) was then added followed by DBU (59.2 , 0.396 mmomulL). The resulting solution was then stirred for another 1.5 hours. Volatiles were evaporated. The remaining residue was taken up in dichloromethane (2 mL) and washed with aqueous 1 M citric acid (1 x 2 mL). The organic layer was injected onto a silica gel column to be purified by chromatography: 12 gram silica gel column, 0-10% MeOH/DCM gradient. 2-chloro-N-(3-fluorophenyl)sulfonyl-6-[3-[(2,2,3,3-tetramethylcyclopropyl)methoxy]pyrazol-l-yl]pyridine-3-carboxamide (150 mg, 70%) was obtained. ESI-MS m/z calc. 506.11908, found 507.0 (M+l)+; Retention time: 2.24 minutes
2-chloro-6-[3-[(2,2,3,3-tetramethylcyclopropyl)methoxy]pyrazol-1-yl]pyridine-3-carboxylic acid[ No CAS ]
N-(3-fluorophenyl)sulfonyl-6-[3-[(2,2,3,3-tetramethylcyclopropyl)methoxy]pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide[ No CAS ]
N-[2-(1-(methoxyimino)ethyl)phenyl]-3-fluorobenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; silver(I) acetate; silver(I) triflimide; In dichloromethane; at 60℃; for 24h;
(1) 0.0040g iridium catalyst [Cp * IrCl2] 2,0.0076 g silver salt bis(trifluoromethanesulfonyl)imide silver,0.825g oxidant silver acetate,31.4muLacetophenone-O-methyl oxime and0.07 g of <strong>[1524-40-9]m-fluorobenzenesulfonamide</strong> was placed in a reaction tube.Add 2mL of dichloromethane as a solvent,Heating and stirring reaction,The temperature of heating and stirring is 60C.Reaction time 24h.(2) After the reaction is over,Separation by column chromatography (300-400 column chromatography silica gel column packing,Eluent: ethyl acetate: petroleum ether = 12:100 v/v),Can get the product N-[2-(1-Methoxyimino)ethyl]phenyl-<strong>[1524-40-9]3-fluorobenzenesulfonamide</strong>.The yield is 83%.The structural characterization of the products are shown in Figures 21 and 22, respectively.
3-fluoro-N-((2-phenylimidazo[1,2-a]pyridin-3-yl)methyl)benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With potassium permanganate; di-tert-butyl peroxide; sodium t-butanolate; at 130℃; for 8h;
Preparation method: in an air environment, 35mL high-pressure tube were added to 2-phenylimidazole and 0.1mmol [1,2-a] pyridine compound,0.2 mmol of <strong>[1524-40-9]3-fluorobenzenesulfonamide</strong>,0.2 mmol of di-tert-butyl peroxide, 0.1 mmol of permanganic acidPotassium, 0.1 mmol of sodium t-butoxide, hexafluoroisopropanol and methanol (volume ratio 1:9) 2 mL, reacted at 130 C for 8 hours; end of reactionAfter chromatography, silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0,Dryed to a yellow solid with a yield of 82%.