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[ CAS No. 32333-53-2 ] {[proInfo.proName]}

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Chemical Structure| 32333-53-2
Chemical Structure| 32333-53-2
Structure of 32333-53-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 32333-53-2 ]

CAS No. :32333-53-2 MDL No. :MFCD00024882
Formula : C7H3Cl2F3O2S Boiling Point : -
Linear Structure Formula :- InChI Key :SSULGNXFUGLULI-UHFFFAOYSA-N
M.W :279.06 Pubchem ID :2780719
Synonyms :

Calculated chemistry of [ 32333-53-2 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 2
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 49.54
TPSA : 42.52 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.03 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.93
Log Po/w (XLOGP3) : 4.18
Log Po/w (WLOGP) : 5.52
Log Po/w (MLOGP) : 3.15
Log Po/w (SILICOS-IT) : 3.08
Consensus Log Po/w : 3.57

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.37
Solubility : 0.012 mg/ml ; 0.0000429 mol/l
Class : Moderately soluble
Log S (Ali) : -4.78
Solubility : 0.00461 mg/ml ; 0.0000165 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -4.44
Solubility : 0.0102 mg/ml ; 0.0000364 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.99

Safety of [ 32333-53-2 ]

Signal Word:Danger Class:8
Precautionary Statements:P234-P260-P264-P280-P301+P330+P331+P310-P303+P361+P353+P310+P363-P304+P340+P310-P305+P351+P338+P310-P390-P405-P406-P501 UN#:3261
Hazard Statements:H290-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 32333-53-2 ]

* 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.

  • Downstream synthetic route of [ 32333-53-2 ]

[ 32333-53-2 ] Synthesis Path-Downstream   1~79

  • 1
  • [ 39662-63-0 ]
  • [ 32333-53-2 ]
  • [ 111711-54-7 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium 1.) THF, hexane, -70 deg C, 45 min, 2.) THF, hexane, -70 deg C, 2 h; Yield given. Multistep reaction;
YieldReaction ConditionsOperation in experiment
1-Chlor-2-trifluormethylbenzol, Cl-SO3H;
1-Chlor-2-trifluormethylbenzol, Chlorsulfonsaeure, Oleum;
1-Chlor-2-trifluormethylbenzol, Chlorsulfonsaeure;
  • 3
  • [ 71-44-3 ]
  • [ 32333-53-2 ]
  • <i>N</i>-{3-[4-(3-amino-propylamino)-butylamino]-propyl}-4-chloro-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 25℃; for 16h;
  • 4
  • [ 956488-93-0 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-(3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With pyridine at 20℃; for 20h;
60% With pyridine at 20℃; for 20h; 120 Synthesis 120; 4-Chloro-N-(3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)- 3-(trifluoromethyl)benzenesulfonamide (CJS 3684); Method K: 7-(3-Aminophenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one (30 mg, 0.13 mmol) was suspended in dry pyridine (3 mL) and 4-chloro-3-(trifluoromethyl)-benzene-1-sulfonyi chloride (44.4 mg, 0.16 mmol) in pyridine (2 mL) was added. The resulting solution was stirred at room temperature for 20 h and subsequently the solvent was removed in vacuo. The obtained residue was dissolved in acetone (4 mL) and upon addition of water a solid precipitated. This solid was collected, washed with water (2 x 2 mL) and Et2O (2 x 2 mL) and dried to afford the title compound as an off-white solid (38 mg, 60%). 1H-NMR (δ, ppm, DMSOd6): 6.23 (d, 1 H, HPy,5, J= 5.78 Hz), 6.76 - 6.98 (m, 3H, Haram), 7.35 (m, 1H, Harom), 7.73 (m, 1 H, Harom), 7.94 - 7.96 (m, 2H1 Harom), 8.05 (d, 1 H, HPy,6, J= 5.78 Hz) 10.62 (s, 1 H, NHSO2), 11.13 (s, 1 H1 NHPy3), 1140 (s, 1H, NHPy2). 13C-NMR (δ, ppm,DMSO-d6): 106.31, 111.11 , 113.80, 115.61, 116.73, 121.97, 125.78, 131.10, 132.18, 132.33, 133.22, 135.76, 138.47, 138.57, 141.13, 144.01, 147.23, 154.15, 155.11. HRMS (El): m/z [M + H] calcd for C19H13CIF3N4O4S: 485.0298; found: 485.0297.
  • 5
  • [ 769169-26-8 ]
  • [ 32333-53-2 ]
  • 4-Chloro-N-(3,3,3-trifluoro-1-hydroxymethyl-2-trifluoromethyl-propyl)-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% With pyridine In dichloromethane at 25℃; for 96h; 4 4-Chloro-N-(3,3,3-trifluoro-1-hydroxymethyl-2-trifluoromethyl-propyl)-3-trifluoromethyl-benzenesulfonamide Example 4 4-Chloro-N-(3,3,3-trifluoro-1-hydroxymethyl-2-trifluoromethyl-propyl)-3-trifluoromethyl-benzenesulfonamide To a solution of 4,4,4,4',4',4'-hexafluoro-dl-valinol (0.10 g, 0.47 mmol) in CH2Cl2 (3 mL) was added a previously dissolved mixture of 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (0.132 g, 0.47 mmol) in CH2Cl2 (1 mL). Pyridine (77 μL, 0.95 mmol) was added and the mixture was stirred at 25° C. for 96 h. The reaction was diluted by adding CH2Cl2 (10 mL) and poured into a separatory funnel. It was then washed sequentially with 1 N HCl (2*), distilled water, brine, and dried over MgSO4 and evaporated to afford the crude product which was purified by flash chromatography, eluent: 3:1 hexanes-ethyl acetate, to afford the product as a solid (35.5 mg, 17%). MS (-ESI) 452.0 ([M-H]-). Anal: Calc'd for C12H9ClF9NO3S.0.13 Hexane C, 33.02; H, 2.35; N, 3.01. Found: C, 33.03; H, 2.10; N, 2.94.
  • 6
  • [ 32333-53-2 ]
  • [ 593-56-6 ]
  • [ 304912-79-6 ]
YieldReaction ConditionsOperation in experiment
92%
  • 7
  • [ 107-10-8 ]
  • [ 32333-53-2 ]
  • [ 731776-57-1 ]
YieldReaction ConditionsOperation in experiment
LXVIII Following the procedure of N. Ikemoto et al. (Tetrahedron, 59:1317 (1998)), 3-chloro-4-trifluoromethylaniline (890 mg, 4.6 mmol, Ryan Scientific) in CH3CN (37 mL) was added to a 250 mL round-bottomed flask. The flask was cooled in an ice bath, and HOAc (3.7 mL) and HCl (12 M, 1.8 mL) were added. Sodium nitrite (380 mg, 5.5 mmol, Aldrich) in 0.77 mL of H2O was added in 0.15 mL portions every 2 min until all of the solution had been added (total time ca. 9 min). After 25 min, sulfur dioxide (Aldrich) was bubbled into the reaction mixture for 1.25 h. Copper(II)chloride (780 mg, 5.8 mmol, Aldrich) in 1.5 mL of water was then added to the reaction mixture. Gas evolution occurred, and the reaction was warmed to RT and stirred overnight. After the lower boiling solvents were removed in vacuo, water was added, and the mixture was extracted with CH2Cl2 (3×). The combined organic layers were washed with water, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as a brownish oil with solid in it. The compound did not ionize well, but an aliquot, when treated with propylamine, provided the propylarylsulfonamide adduct with a ESI-MS, -ion, m/z=300.2 (M-1).
  • 8
  • [ 445-13-6 ]
  • [ 32333-53-2 ]
YieldReaction ConditionsOperation in experiment
Following the procedure of N. Ikemoto et al. (Tetrahedron, 59:1317 (1998)), <strong>[445-13-6]3-chloro-4-trifluoromethylaniline</strong> (890 mg, 4.6 mmol, Ryan Scientific) in CH3CN (37 mL) was added to a 250 mL round-bottomed flask. The flask was cooled in an ice bath, and HOAc (3.7 mL) and HCl (12 M, 1.8 mL) were added. Sodium nitrite (380 mg, 5.5 mmol, Aldrich) in 0.77 mL of H2O was added in 0.15 mL portions every 2 min until all of the solution had been added (total time ca. 9 min). After 25 min, sulfur dioxide (Aldrich) was bubbled into the reaction mixture for 1.25 h. Copper(II)chloride (780 mg, 5.8 mmol, Aldrich) in 1.5 mL of water was then added to the reaction mixture. Gas evolution occurred, and the reaction was warmed to RT and stirred overnight. After the lower boiling solvents were removed in vacuo, water was added, and the mixture was extracted with CH2Cl2 (3×). The combined organic layers were washed with water, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as a brownish oil with solid in it. The compound did not ionize well, but an aliquot, when treated with propylamine, provided the propylarylsulfonamide adduct with a ESI-MS, -ion, m/z=300.2 (M-1).
  • 9
  • [ 899423-98-4 ]
  • [ 32333-53-2 ]
  • N-(2-benzoyl-5-chloro-pyridin-3-yl)-4-chloro-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; dmap at 60℃; for 96h; 22 Example 22: N-(2-Benzoyl-5-chloro-pyridin-3-ylV4-chloro-3-trifluoromethyl- benzene sulfonamide; [00406] A solution of (3-amino-5-chloro-pyridin-2-yl)-phenyl-methanone (40 mg, 0.17 mmol), 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (72 mg, 0.26 mmol), and DMAP (11 mg, 0.09 mmol) in anhydrous pyridine (0.5 mL) was heated at 60 °C for 4 days. The product was separated by preparative HPLC and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCI3) 610.56 (s, 1 H), 8.39 (s, 1 H), 8.17 (s, 1 H), 8.07 (s, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.54 (d, J = 7.6 Hz, 2 H), 7.61-7.58 (m, 1 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.45-7.42 (m, 2 H); MS m/z : 475.0 (M+H).
  • 10
  • [ 874491-64-2 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-(5-chloro-2-phenoxy-pyridin-3-yl)-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; for 5h; 18 Example 18: 4-Chloro-N-(5-chloro-2-phenoxy-pyridin-3-yl)-3-trifluoromethyl- benzene sulfonamide; [00402] To a solution of 5-chloro-2-phenoxy-pyridin-3-ylamine (60 mg, 0.27 mmol) in anhydrous pyridine (0.5 mL) was added drop wise a solution of 4- chloro-3-trifluoromethyl-benzenesulfonyl chloride (76 mg, 0.27 mmol) in pyridine (0.5 mL). The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was separated by preparative HPLC using acetonitrile-water solvent mixture and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCI3) δ 8.14 (s, 1 H), 7.89-7.87 (m, 2 H), 7.81 (m, 1 H), 7.59 (d, J = 8.0 Hz, 1 H), 7.35 (t, J = 8.4 Hz, 1 H), 7.25-7.19 (m, 2 H), 6.76 (d, J = 8.0 Hz, 2 H). MS m/z : 463.0 (M+H).
  • 11
  • [ 899424-00-1 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-[5-chloro-2-(2-fluoro-phenoxy)-pyridin-3-yl]-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; dmap at 20℃; for 48h; 20 Example 20: 4-Chloro-N-[5-chloro-2-(2-fluoro-phenoxy)-pyridin-3-vfl-3- trifluoromethyl-benzenesulfonamide; [00404] A solution of 5-chloro-2-(2-fluoro-phenoxy)-pyridin-3-ylamine (75 mg, 0.31 mmol), 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (103 mg, 0.36 mmol), DMAP (20 mg, 0.16 mmol) in anhydrous pyridine (1 mL) was stirred at room temperature for 2 days. The reaction product was separated by preparative HPLC using acetonitrile-water solvent mixture and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCI3) δ 8.16 (s, 1 H), 7.96 (s, 1 H), 7.89 (d, J = 8.0 Hz, 1 H), 7.79 (s, 1 H), 7.62 (d, J = 8.0 Hz, 1 H), 7.15-7.13 (m, 3 H), 7.00-6.96 (m, 1 H). MS m/z : 481.0 (M+H).
  • 12
  • [ 899424-02-3 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-[5-chloro-2-(4-fluoro-phenoxy)-pyridin-3-yl]-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; dmap at 20℃; for 48h; 21 Example 21 : 4-Chloro-N-r5-chloro-2-(2-fluoro-phenoxy)-pyridin-3-yl]-3- trifluoromethyl-benzenesulfonamide; [00405] A solution of 5-chloro-2-(4-fluoro-phenoxy)-pyridin-3-ylamine (75 mg, 0.31 mmol), 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (103 mg, 0.36 mmol), DMAP (20 mg, 0.16 mmol) in anhydrous pyridine (1 mL) was stirred at room temperature for 2 days. The reaction mixture was separated by preparative HPLC and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCI3) δ 8.16 (s, 1 H), 7.92-7.90 (m, 2 H), 7.81 (s, 1 H), 7.64 (d, J = 7.6 Hz, 1 H), 7.11 (s, 1 H), 7.06-7.03 (m, 2 H), 6.76- 6.74 (m, 2 H). Mass spectrum m/z : 481.0 (M+H).
  • 13
  • [ 899424-04-5 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-[5-chloro-2-(pyridin-4-ylsulfanyl)-pyridin-3-yl]-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 5-chloro-2-(pyridin-4-ylsulfanyl)-pyridin-3-ylamine; 4-chloro-3-trifluoromethylbenzenesulfonyl chloride With pyridine at 20℃; for 48h; Stage #2: With sodium hydroxide In water Stage #3: With hydrogenchloride In water 19 Example 19: 4-Chloro-N-[5-chloro-2-(pyridin-4-ylsulfanyl)-pyridin-3-yl]-3- trifluoromethyl-benzenesulfonamide; [00403] To a solution of 5-chloro-2-(pyridin-4-ylsulfanyl)-pyridin-3-ylamine (100 mg, 0.42 mmol) in anhydrous pyridine (0.5 mL) was added drop wise a solution of 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (117 mg, 0.42 EPO mmol) in pyridine (0.25 mL). The resulting mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure and diluted with EtOAc and brine. The aqueous portion was separated and extracted with EtOAc. The combined extracts were dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was treated with 0.3 M aqueous NaOH and washed with CH2CI2. The aqueous portion was acidified with cone HCI to pH 3 and extracted with EtOAc. The combined extracts were dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was separated by preparative HPLC (20 → 80% gradient of ACN-water) and pure product fractions were lyophilized to provide pure product as a solid. Mass spectrum m/z : 480.0 (M+H).
  • 14
  • [ 899424-10-3 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-[5-chloro-2-(pyridine-3-carbonyl)pyridin-3-yl]-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; dmap at 60℃; for 48h; 23 Example 23: 4-Chloro-N-[5-chloro-2-(pyridine-3-carbonylVpyridin-3-yl]-3- trifluoromethyl-benzenesulfonamide; [00407] A solution of (3-amino-5-chloro-pyridin-2-yl)-pyridin-3-yl-methanone (26 mg, 0.11 mmol), 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (28 mg, 0.10 mmol), DMAP (7.3 mg, 0.06 mmol) in anhydrous pyridine (0.5 mL) was heated at 60 °C for 2 days. The reaction mixture was separated by preparative HPLC and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCI3) δ 11.03 (s, 1 H), 9.15 (s, 1 H), 8.81-8.80 (m, 1 H), 8.37 (d, J = 2.0 Hz, 1 H), 8.29-8.26 (m, 1 H), 8.20-8.18 (m, 2 H), 7.98 (dd, J = 8.4, 2.8 Hz, 1 H), 7.63 (d, J = 8.4 Hz, 1 H), 7.51-7.48 (m, 1 H). Mass spectrum m/z : 476.0 (M+H).
  • 15
  • [ 90902-83-3 ]
  • [ 32333-53-2 ]
  • [ 899422-52-7 ]
YieldReaction ConditionsOperation in experiment
Example 24: N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-3-trifluoromethyl- benzenesulfonamide; [00408] A mixture of 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (1.5 g, 5.3 mmol) and <strong>[90902-83-3]2-bromo-5-chloro-pyridin-3-ylamine</strong> (500 mg, 2.4 mmol) dissolved in pyridine (20 mL) was heated at 60 C for 16 h. The solvent was evaporated and the residue suspended in a 1 :1 mixture of 2 M NaOH and methanol (20 mL) and heated at 70 C for 30 min. The methanol was evaporated under reduced pressure and the residue diluted with 15 mL water. The solution was cooled on ice bath and the pH was adjusted to 3 by drop wise addition of concentrated HCI. The solid formed was collected by filtration and the product was purified by flash chromatography on silica gel column to afford the desired product. MS m/z : 450.8 (M+H).
  • 16
  • [ 32333-53-2 ]
  • [ 34552-14-2 ]
  • [ 899424-65-8 ]
YieldReaction ConditionsOperation in experiment
84% With pyridine; at 60℃; for 12.0h; Example 173: N-(2-Bromo-5-methyl-pyridin-3-yl)-4-chloro-3-trifluoromehtyl benzenesulfonamide; [00580] A solution of 2-bromo-5-mehtyl-pyridin-3-ylamine (1 g, 5.38 mmol) and 4-chloro-3-trifluoromethylbenzenesulfonylchloride (1.8 g, 6.46 mmol) in pyridine (5 mL) was stirred at 60 C for 12 h. The mixture was concentrated EPO <DP n="208"/>under reduced pressure and to it, was added 1 :1 EtOAc-10% aqueous HCI (50 mL). Aqueous layer was separated and extracted with EtOAc (2 x 50 mL). Combined EtOAc layers were washed with 10% aqueous HCI (50 mL), dried (anhydrous Na2SO4), concentrated and column purified (SiO2, 50% EtOAc- hexanes) to obtain N-(2-bromo-5-methyl-pyridin-3-yl)-4-chloro-3-trifluoromehtyl- benzenesulfonamide (1.42 g) in 84% yield as a half white solid. ESMS m/z (relative intensity): 429 (M+H)+ (100).
  • 17
  • [ 408538-29-4 ]
  • [ 32333-53-2 ]
  • C13H6Cl2F3N3O2S [ No CAS ]
  • C13H8Cl2F3N3O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 70℃; for 5h; 121.3 Step 3: A 500 mL round-bottom flask was charged with the above 3-amino-2-cyano-5-chloropyridine (7.7 g, 50 mmol), 4-CI-3-trifluoromethyl- benzenesulfonyl chloride (28 g, 100 mmol), and pyridine (50 mL). The resultant solution was heated to 70 °C and stirred for 5 h. The pyridine was removed in vacuo and EtOH (80%, 260 mL) was added, followed by NaOH (30 g, 0.75 mol). The mixture was heated at reflux for 12 h. The solvent was subsequently removed in vacuo and ice (100 g) was added and the pH adjusted to 2-3 with cone HCI. The resultant aqueous solution was extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The EPO resultant light yellow solid was further crystallized from EtOAc/hexane (1 :1) to afford 5-chloro-3-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)picolinic acid as white needles (10 g, 44% overall): 1H NMR (400 MHz, CDCI3) δ 10. 80 (s, 1 H), 8.23 (m, 3H), 8.00 (d, 1 H), 7.63 (d, 1 H); MS (ES) 415.0 (M+H).
  • 18
  • [ 93-67-4 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-(5-chloro-2-phenoxy-phenyl)-3-trifluoromethyl-benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; for 2h; 17 Example 17: 4-Chloro-N-(5-chloro-2-phenoxy-phenyl)-3-trifluoromethyl- benzenesulfonamide; [00401] To a solution of 5-chloro-2-phenoxy-phenylamine (75 mg, 0.34 mmol) in anhydrous pyridine (0.5 mL) was added drop wise a solution of 4- chloro-3-trifluoromethyl-benzenesulfonyl chloride (95 mg, 0.341 mmol) in pyridine (0.5 mL). The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was separated by preparative HPLC using acetonitrile-water solvent mixture and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCI3) δ 8.04 (d, J = 2.0 Hz, 1 H), 7.80 (dd, J = 8.4, 2.0 Hz, 1 H), 7.70 (d. J = 2.4 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1 H), 7.27-7.23 (m, 2 H), 7.14-7.10 (m, 1 H), 7.05-7.02 (m, 2 H), 6.66 (d, J = 8.4 Hz, 1 H), 6.60-6.56 (m, 2 H). MS m/z : 484.0 (M+Na).
With pyridine at 20℃; 1 Example 14-Chloro-N-(5-chloro-2-phenoxy-phenyl)-3-trifluoromethyl-benzenesulfonamide To a solution of 5-chloro-2-phenoxy-phenylamine (75 mg, 0.34 mmol) in anhydrous pyridine (0.5 mL) was added drop wise a solution of 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (95 mg, 0.341 mmol) in pyridine (0.5 mL). The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was separated by preparative HPLC (20→80% gradient of ACN-water) and pure product fractions were lyophilized to provide pure product as a solid. 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J=2.0 Hz, 1H), 7.80 (dd, J=8.4, 2.0 Hz, 1H), 7.70 (d, J=2.4 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 7.27-7.23 (m, 2H), 7.14-7.10 (m, 1H), 7.05-7.02 (m, 2H), 6.66 (d, J=8.4 Hz, 1H), 6.60-6.56 (m, 2H). MS m/z: 484.0 (M+Na).
  • 19
  • [ 16298-03-6 ]
  • [ 32333-53-2 ]
  • [ 899424-20-5 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; for 16h; 42.1 Example 42: 4-Chloro-N-r3-(morpholine-4-carbonyl)-pyrazin-2-yl]-3- trifluoromethyl-benzenesulfonamide; [00431] Step 1 : To a solution of 3-amino-pyrazine-2-carboxylic acid methyl ester (153 mg, 1.0 mmol) in 2.0 mL of pyridine was added 4-chloro-3- trifluoromethyl-benzenesulfonyl chloride (279 mg, 1.0 mmol) in 1.0 mL of pyridine. The mixture was stirred at room temperature for 16 h, diluted with 15 mL of ethyl acetate, washed twice with 1 M HCI (15 mL), dried on MgSO4 and the solvent was evaporated. The product was purified on silica gel column (15% ethyl acetate in hexane) to afford 185 mg of 3-(4-chloro-3-trifluoromethyl- benzenesulfonylamino)-pyrazine-2-carboxylic acid methyl ester as white powder. MS: (M + H) / z = 396.0.
  • 20
  • 4-[4-(3-amino-[1,2,4]triazin-5-yl)-phenoxy]-pyridine-2-carboxylic acid methylamide [ No CAS ]
  • [ 32333-53-2 ]
  • 4-{4-[3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-[1,2,4]triazin-5-yl]-phenoxy}-N-methylpyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20 - 100℃; for 1 - 2h; 104 108.6 mg (0.337 mmol, 1.0 equivalent) of 4-[4-(3-amino-[l,2,4]triazin-5-yl)-phenoxy]-N-methylpyridine-2-carboxamide can be dissolved in 2 mL of anhydrous pyridine with heating to about 100 °C. 0.405 mmol (1.2 equivalent) bf 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride can be added. The reaction mixture can be allowed to stir at ambient temperature for 1-2 hours. The product can be isolated by a number of methods known to one skilled in the art, such as precipitation or by extraction with a number of solvents, such as ethyl acetate, methylene chloride or diethyl ether or by silica gel column chromatography, or by reverse-phase preparative HPLC.
  • 21
  • [ 884339-96-2 ]
  • [ 32333-53-2 ]
  • N-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)-3-(trifluoromethyl)-4-chlorobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With pyridine at 20℃; for 20h; XVII.113.N (XVlI) Synthesis of sulfonamides; Synthesis 113; 4-Chloro-N-(4-(2-oxo-2,3-dihydro-1 H-imidazo[4,5-/)]pyridin-7-yl-oxy)phenyl)-3- (trifluoromethyl)benzenesulfonamide (CJS 3650); Method N. 7-(4-Aminophenoxy)-2,3-dihydro-2-oxo-1H-imidazo[4,5-jb]pyridine (30 mg, 0.13 mmol) was suspended in dry pyridine (3 ml.) and 4-chloro-3-(trifluoro methyl)benzene-1-sulfonyl chloride (44.4 mg, 0.16 mmol) was added. The resulting solution was stirred at room temperature for 20 hours and subsequently the solvent was removed in vacuo. The obtained residue was dissolved in acetone (4 ml_) and upon addition of water a solid precipitated. This solid was collected, washed with water (2 x 2 ml_) and Et2O (2 x 2 ml_) and dried to give the title compounds as an off-white solid (44 mg, 57%). 1H-NMR (δ, ppm, DMSO-d6): 6.28 (d, 1H, HPy,5, J = 5.8 Hz), 7.12 (s, 4H, Harom,Ph), 7.75 (d, 1 H, HPy,6), 7.98 (s, 2H, Harom,Ph.), 8.05 (s, 1 H, Harom,ph.), 10.47 (s, 1H, NHSO2), 11.17 (s, 1 H, NHPy3), 11.40 (s, 1H, NHPy2). LC-MS (m/z): 485 (M + H, 100).
57% With pyridine at 20℃; for 20h;
  • 22
  • [ 32333-53-2 ]
  • [ 6397-33-7 ]
  • 4-Chloro-3-trifluoromethyl-2-isopropylthiobenzensulfonanilide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 12 4-Chloro-3-trifluoromethyl-2--isopropylthiobenzensulfonanilide (Compound No. 66) The procedure of Example 10 was repeated using 16.7 g of <strong>[6397-33-7]2-isopropylthioaniline</strong> and 27.9 g of 4-chloro-3-trifluoromethylbenzenesulfonyl chloride to yield 37.7 g of the title compound as a brown oil. Purification by silicagel-colum chromatography gave a colorless oil, n [23/D ] =1.5518.
  • 23
  • [ 32333-53-2 ]
  • [ 2987-53-3 ]
  • 3-trifluoromethyl-4-chloro-2-methylthiobenzenesulfonanilide [ No CAS ]
YieldReaction ConditionsOperation in experiment
11 4-Chloro-3-trifluoromethyl-2--methylthiobenzene sulfonanilide (Compound No. 58) Example 11 4-Chloro-3-trifluoromethyl-2--methylthiobenzene sulfonanilide (Compound No. 58) The procedure of Example 10 was repeated using 13.9 g of 2-methylthioaniline and 27.9 g of 4-chloro-3-trifluoromethylbenzenesulfonyl chloride to yield 35.9 g of the title compound as pale brown crystals. Recrystallization from hexane-ethyl acetate gave white crystals, m.p. 90-92°C.
  • 24
  • [ 32333-53-2 ]
  • [ 89-77-0 ]
  • [ 756851-01-1 ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: 4-chloro-3-trifluoromethylbenzenesulfonyl chloride; 2-Amino-4-chlorobenzoic acid With sodium carbonate In 1,4-dioxane; water at 60 - 80℃; for 4h; Stage #2: With hydrogenchloride In 1,4-dioxane; water [00253] To a solution of Na2CO3 (11 7 g, 110 7 mmol) in water (50 ml_) and 1 ,4-dιoxane (50 mL) at 60 0C was added 2-amιno-4-chloro-benzoιc acid (5 0 g, 29 14 mmol) followed by 4-chloro-3-trιfluoromethyl-benzenesulfonyl chloride (20 15 g, 72 48 mmol) in 3 portions and heated the resulting reaction mixture at 80 0C for 4 hours 2N HCI Was added until the reaction mixture became acidic (pH = ~2) and obtained white solid was filtered, washed with water, dried under high vacuum to obtain title compound (7 8 g) in 65% yield MS (ES) M+Na expected 436 0, found 435 8
  • 25
  • [ 408538-29-4 ]
  • [ 32333-53-2 ]
  • C13H6Cl2F3N3O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 70℃; for 5h; 3 A 100 mL round-bottom flask was charged with the above 3-amιno-2-cyano-5-chloropyrιdιne mixture (7 7 g, 50 mmol), 4-chloro-3- trifluoromethylbenzenesulfonyl chloride (28 g, 100 mmol), and pyridine (50 mL). The resultant solution was heated to 70 "C and stirred for 5 hours. The pyridine was removed in vacuo and 80% aq. EtOH (260 mL) was added, followed by NaOH (30 g, 0.75 mol). The mixture was stirred under reflux for 12 hours. The solvent was subsequently removed in vacuo and ice (100 g) was added. The pH adjusted to 2-3 with cone. HCI. The resultant aqueous solution was extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated in vacuo. The resulting light yellow solid was recrystallized from EtOAc/hexane ( 1 : 1 ) to afford the desired acid as white needles (10 g, 44% overall yield): 1H NMR (400 MHz, CDCI3) δ 10.80 (s, 1 H), 8.23 (m, 3H), 8.00 (d, 1 H), 7.63 (d, 1 H); MS (ES) (M+H)+ expected 415.0, found 415.0.
  • 26
  • [ 1001635-30-8 ]
  • [ 32333-53-2 ]
  • 3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-5-methyl-pyridine-2-carbonitrile sodium salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% Stage #1: 3-amino-5-methylpyridine-2-carbonitrile; 4-chloro-3-trifluoromethylbenzenesulfonyl chloride With pyridine at 60℃; for 13h; Stage #2: With sodium hydroxide In tetrahydrofuran; water at 0℃; for 0.833333h; 13.a [00347] To a solution of 3-amino-2-cyano-5-methylpyridine (83 g, 0.619 mol) in pyridine (625 ml_) was added 4-chloro-3- trifluoromethylbenzenesulfonyl chloride (207 g, 0.742 mol) in one portion and the resulting reaction mixture stirred at 60 0C over night (13 hours). Pyridine was removed in vacuo, THF (350 ml_) was added and removed in vacuo. To the obtained dark brown solid was added THF (650 ml_), H2O (550 mL), followed by NaOH (75 g, 1.88 mol) slowly at 0 °C (in five portions) over 20 minutes. The resulting solution was stirred at 0 0C for another 30 minutes. After removing THF in vacuo (~ 650 mL), H2O (50 mL) was added and the suspension was heated to dissolve all the solids. After cooling in an ice bath for 2 hours, the resulting solid was collected by filtration, washed with ice water (100 mL X 3) and dried in a 1 10 °C vacuum oven for 24 hours to afford the title compound (190 g, 77%) as white needles: mp. 287.0 - 288.5.0C. 1H NMR (400 MHz, d6-DMSO) δ 8.05 (1 H, s), 7.96 (d, 1 H), 7.76 (dd, 1 H), 7.63 (s, 1 H), 7.40 (s, 1 H), 2.12 (s, 3H). MS (ES) M+H expect 375.9, found 375.9. Mother liquor was concentrated (~ 2/3 volume) in vacuo to afford another 30 g of the title compound after washing and drying, total yield 89%.
  • 27
  • [ 1001635-30-8 ]
  • [ 32333-53-2 ]
  • [ 1100318-71-5 ]
  • C21H11Cl2F6N3O4S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 60℃; [00264] To 3-amino-5-methylpicolinonitrile (9.6g, 72 mmol) in pyridine (63 ml_) was added 4-chloro-3-trifluoiOmethyl-benzenesulfonyl chloride (19.6 g, 80 mmol) in one portion and the resulting reaction mixture was stirred at 60 °C for overnight. Pyridine was removed in vacuo, added 2N HCI (100 ml_), extracted with EtOAc (3 x 300 ml Note: due to the amide presence, solubility in EtOAc is low). Combined EtOAc layers were dried (Na2SO4), evaporated to obtain 26.3 g of crude product which contained a small amount of bis- sulfonamide which was subjected to hydrolysis in THF (200 ml.) with 2N NaOH (100 mL) at room temperature for 2 hours. 2 N HCI (100 ml_) Was added, extracted with EtOAc (1 x 700 mL, 1x 250 mL), combined EtOAc layers were washed with saturated NaHCO3 solution (2 x 250 mL), dried (Na2SO4) and evaporated to obtain 22 g of monosulfonamide. To this dioxane (350 mL), water (450 mL) (Note: requires high dilution for fast reaction) was added, followed by NaOH (30 g, 0.75 mol) and stirred under reflux for 24 hours. Dioxane was removed in vacuo and cone. HCI (75 mL) was added slowly with cooling. The resultant solid was filtered, washed with water and dried in vacuo to afford title compound (22 g, 88% for 2 steps) as light yellow solid. (M+H) Expected: 395.0; found 394.9.
  • 28
  • [ 445-13-6 ]
  • [ 7446-09-5 ]
  • [ 32333-53-2 ]
YieldReaction ConditionsOperation in experiment
Following the procedure of N. Ikemoto et al. (Tetrahedron, 59 : 1317 (1998)), <strong>[445-13-6]3-chloro-4-trifluoromethylaniline</strong> (890 mg, 4.6 mmol, Ryan Scientific) in CH3CN (37 mL) was added to a 250 mL round-bottomed flask. The flask was cooled in an ice bath, and HOAc (3.7 mL) and HCl (12 M, 1.8 mL) were added. Sodium nitrite (380 mg, 5.5 mmol, Aldrich) in 0.77 mL of H2O was added in 0.15 mL portions every 2 min until all of the solution had been added (total time ca. 9 min). After 25 min, sulfur dioxide (Aldrich) was bubbled into the reaction mixture for 1.25 h. Copper (II) chloride (780 mg, 5.8 mmol, Aldrich) in 1.5 mL of water was then added to the reaction mixture. Gas evolution occurred, and the reaction was warmed to RT and stirred overnight. After the lower boiling solvents were removed in vacuo, water was added, and the mixture was extracted with CH2Cl2 (3x). The combined organic layers were washed with water, dried over MgSO4, filtered and concentrated in vacuo to give the crude material as a brownish oil with solid in it. The compound did not ionize well, but an aliquot, when treated with propylamine, provided the propylarylsulfonamide adduct with a ESI-MS,-ion, M/Z = 300.2 (M-1).
  • 29
  • [ 114995-70-9 ]
  • [ 32333-53-2 ]
  • [ 1001326-25-5 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; Cooling with ice; 4 Example 44-Chloro-N-[5-chloro-2-(pyridine-4-carbonyl)-phenyl]-3-trifluoromethylbenzenesulfonamide To an ice-water cooled solution of 2-amino-4-chloro-phenyl-pyridin-4-yl-methanone (40 mg, 0.17 mmol) in pyridine (1.0 mL) was added 4-chloro-3-trifluoromethylbenzenesulfonylchloride (48 mg, 0.17 mmol) in pyridine (0.5 mL). The mixture was stirred at room temperature for 3 hours. The mixture was diluted with ethyl acetate, washed with water and dried. After concentration the residue was purified via flash column (50% ethyl acetate in hexane) to give 4-chloro-N[5-chloro-2-(pyridine-4-carbonyl)-phenyl]-3-trifluoromethylbenzenesulfonamide as a white powder. 1H-NMR (400 MHz, CDCl3): δ 8.73 (d, 2H), 7.95 (d, 1H), 7.80 (m, 1H), 7.67 (m, 1H), 7.52-7.49(m, 2H), 7.45 (m, 1H), 7.37 (m, 1H) MS: (M+H)/z=475.0.
  • 30
  • [ 791098-01-6 ]
  • [ 32333-53-2 ]
  • [ 1001326-28-8 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; Cooling with ice; 7 Example 74-Chloro-3-trifluoromethyl-N-[5-chloro-2-(piperidine-1-carbonyl)-phenyl]benzenesulfonamide To an ice-water cooled solution of (2-amino-4-chloro-phenyl)-piperidin-1-yl-methanone (170 mg, 0.71 mmol) in pyridine (1.0 mL) was added 4-chloro-3-trifluoromethylbenzenesulfonylchloride (191 mg, 0.71 mmol) in pyridine (0.5 mL). The mixture was stirred at room temperature for 3 hours. The mixture was diluted with ethyl acetate, washed with water and dried. After concentration the residue was purified via flash column (60% ethyl acetate in hexane) to give of 4-chloro-3-trifluoromethyl-N-[5-chloro-2-(piperidine-1-carbonyl)-phenyl]benzenesulfonamide as a white powder. 1H-NMR (400 MHz, CDCl3): δ 8.88 (s, 1H), 8.13 (s, 1H), 7.94 (m, 1H), 7.67-7.55 (m, 2H), 7.08 (m, 2H), 3.60-3.21 (m, 4H), 1.79-1.32 (m, 6H). MS: (M+H)/z =481.1.
  • 31
  • (2-amino-4-chlorophenyl)(morpholino)methanone [ No CAS ]
  • [ 32333-53-2 ]
  • [ 1001326-27-7 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; Cooling with ice; 6 Example 64-Chloro-3-trifluoromethyl-N-[5-chloro-2-(morpholine-4-carbonyl)-phenyl]benzenesulfonamide To an ice-water cooled solution of (2-amino-4-chloro-phenyl)-morpholin-4-yl-methanone (170 mg, 0.71 mmol) in pyridine (1.0 mL) was added 4-chloro-3-trifluoromethylbenzenesulfonylchloride (191 mg, 0.71 mmol) in pyridine (0.5 mL). The mixture was stirred at room temperature for 3 hours. The mixture was diluted with ethyl acetate, washed with water and dried. After concentration the residue was purified via flash column (60% ethyl acetate in hexane) to give 113 mg of 4-chloro-3-trifluoromethyl-N-[5-chloro-2-(morpholine-4-carbonyl)-phenyl]benzenesulfonamide as a white powder. 1H-NMR (400 MHz, CDCl3): δ 8.80 (s, 1H), 8.15 (s, 1H), 7.96 (d, 1H), 7.65-7.60 (m, 2H), 7.25-7.10 (m, 2H), 3.78-3.10 (m, 8H). MS: (M+H)/z=483.0.
  • 32
  • [ 32333-53-2 ]
  • [ 108-42-9 ]
  • [ 612041-86-8 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; 22 Example 224-Chloro-N-(3-chloro-phenyl)-3-trifluoromethyl-benzenesulfonamide To a solution of 3-chloroaniline (64 mg, 0.50 mmol) in dry pyridine (0.5 mL) was added dropwise a solution of 4-chloro-3-trifluoromethyl)benzenesulfonyl chloride (139 mg, 0.50 mmol) in dry pyridine (0.5 mL). The reaction was stirred overnight at room temperature (complete by LCMS). The reaction was added to a mixture of ice and dilute HCl, and the aqueous mixture was extracted with ethyl acetate (3 X 30 mL). The extracts were dried (MgSO4), filtered and concentrated. The syrup was chromatographed on silica gel using EtOAc-hexane (5:95, 10:90, 15:85) and pure product fractions were concentrated to provide 4-chloro-N-(3-chloro-phenyl)-3-trifluoromethyl-benzenesulfonamide as a white crystalline solid. 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, 1H, J=2.2 Hz), 7.82 (dd, 1H, J=8.4 Hz, J=2.2 Hz), 7.60 (d, 1H, J=8.4 Hz), 7.21 (t, 1H, J=7.8 Hz), 7.15 (dm, 1H, J=7.8 Hz), 7.11 (t, 1H, J=2.0 Hz), 6.95 (ddd, 1H, J=7.8 Hz, J=2.0 Hz, J=1.1 Hz), 6.65 (s, 1H). MS m/z 371.1 (M+1).
  • 33
  • [ 32333-53-2 ]
  • [ 106-47-8 ]
  • [ 2710-06-7 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; 23 Example 234-Chloro-N-(4-chloro-phenyl)-3-trifluoromethyl-benzenesulfonamide To a solution of 4-chloroaniline (64 mg, 0.50 mmol) in dry pyridine (0.5 mL) was added dropwise a solution of 4-chloro-3-trifluoromethyl)benzenesulfonyl chloride (139 mg, 0.50 mmol) in dry pyridine (0.5 mL). The reaction was stirred overnight at room temperature (complete by LCMS). The reaction was added to a mixture of ice and dilute HCl, and the aqueous mixture was extracted with ethyl acetate (3×30 mL). The extracts were dried (MgSO4), filtered and concentrated. The syrup was chromatographed on silica gel using EtOAc-hexane (5:95, 10:90, 15:85) and pure product fractions were concentrated to provide 4-chloro-N-(4-chloro-phenyl)-3-trifluoromethyl-benzenesulfonamide as a white crystalline solid. 1H-NMR (400 MHz, CDCl3): δ 8.05 (d, 1H, J=2.2 Hz), 7.75 (dd, 1H, J=8.4 Hz, J=2.2 Hz), 7.58 (d, 1H, J=8.4 Hz), 7.25 (m, 2H), 7.01 (m, 2H), 6.60 (s, 1H). MS m/z 371.1 (M+1).
  • 34
  • (2-amino-4-chloro-phenyl)-pyrrolidin-1-yl-methanone [ No CAS ]
  • [ 32333-53-2 ]
  • [ 1001326-29-9 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; Cooling with ice; 8 Example 84-Chloro-3-trifluoromethyl-N-[5-chloro-2-(pyrrolidine-1-carbonyl)-phenyl]benzenesulfonamide To an ice-water cooled solution of (2-amino-4-chloro-phenyl)-piperidin-1-yl-methanone (165 mg, 0.71 mmol) in pyridine (1.0 mL) was added 4-chloro-3-trifluoromethylbenzenesulfonylchloride (191 mg, 0.71 mmol) in pyridine (0.5 mL). The mixture was stirred at room temperature for 3 hours. The mixture was diluted with ethyl acetate, washed with water and dried. After concentration the residue was purified via flash column (60% ethyl acetate in hexane) to give 4-chloro-3-trifluoromethyl-N-[5-chloro-2-(pyrrolidine-1-carbonyl)-phenyl]benzenesulfonamide as a white powder. 1H-NMR (400 MHz, CDCl3): δ 8.88 (s, 1H), 8.13 (s, 1H), 7.94 (m, 1H), 7.67-7.55 (m, 2H), 7.08 (m, 2H), 3.60-3.21 (m, 4H), 1.79-1.32 (m, 4H). MS: (M+H)/z=467.0.
  • 35
  • [ 32333-53-2 ]
  • [ 113623-77-1 ]
  • [ 1001326-26-6 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; Cooling with ice; 5 Example 54-Chloro-N-[5-chloro-2-pyridin-2-yl-phenyl]-3-trifluoromethylbenzenesulfonamide To an ice-water cooled solution of 5-chloro-2-(2-pyridin-yl)-aniline (42 mg, 0.20 mmol) in pyridine (1.0 mL) was added 4-chloro-3-trifluoromethylbenzenesulfonylchloride (57 mg, 0.20 mmol) in pyridine (0.5 mL). The mixture was stirred at room temperature for 3 hours. The mixture was diluted with ethyl acetate, washed with water and dried. After concentration the residue was purified via flash. column (30% ethyl acetate in hexane) to give 4-chloro-N-[5-chloro-2-pyridin-2-yl-phenyl]-3-trifluoromethylbenzenesulfonamide as a white powder. 1H-NMR (400 MHz, CDCl3): δ 11.98 (s, 1H), 8.60 (s, 1H), 7.76-7.62 (m, 3H), 7.45-7.25 (m, 6H). MS: (M+H)/z=447.2.
  • 36
  • [ 870532-67-5 ]
  • [ 32333-53-2 ]
  • [ 1001326-35-7 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; 14 Example 144-chloro-N-[4,5-difluoro-2-(pyridine-3-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide To a solution of the starting aminoketone (47 mg, 0.20 mmol) in dry pyridine (0.5 mL) was added dropwise a solution of 4-chloro-3-trifluoromethyl)benzenesulfonyl chloride (57 mg, 0.20 mmol) in dry pyridine (0.3 mL). The reaction was shaken overnight at room temperature. The reaction was separated by preparative HPLC (20→80% gradient of acetonitrile-water) and the pure product fractions were lyophilized to provide 4-chloro-N-[4,5-difluoro-2-(pyridine-3-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide as a light yellow solid. 1H-NMR (400 MHz, CDCl3): δ 10.20 (br s, 1H), 8.79 (dd, 1H, J=4.8 Hz, J=1.4 Hz), 8.61 (d, 1H, J=1.9 Hz), 7.98 (m, 1H), 7.78 (dm, 1H, J=8.4 Hz), 7.72 (dm, 1H, J=7.7 Hz), 7.57 (m, 1H), 7.39 (m, 2H), 7.19 (m, 1H). MS m/z: 477.3 (M+1).
  • 37
  • [ 1001327-24-7 ]
  • [ 32333-53-2 ]
  • [ 1001326-36-8 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; 15 Example 154-Chloro-N-[4-chloro-2-(oxazole-4-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide To a solution of the starting aminoketone (44 mg, 0.20 mmol) in dry pyridine (0.5 mL) was added dropwise a solution of 4-chloro-3-trifluoromethyl)benzenesulfonyl chloride (57 mg, 0.20 mmol) in dry pyridine (0.3 mL). The reaction was shaken overnight at room temperature. The reaction was separated by preparative HPLC (20→80% gradient of ACN-water) and the pure product fractions were lyophilized to provide 4-chloro-N-[4-chloro-2-(oxazole-4-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide as a light yellow solid: 1H-NMR (400 MHz, CDCl3): δ 10.22 (s, 1H), 8.34 (d, 1H, J=2.2 Hz), 8.27 (d, 1H, J=1.1 Hz), 8.00 (d, 1H, J=2.2 Hz), 7.94 (d, 1H, J=1.1 Hz), 7.72 (dd, 1H, J=8.4 Hz, J=2.2 Hz), 7.53 (dd, 1H, J=8.8 Hz, J=2.2 Hz), 7.46 (d, 1H, J=8.4 Hz). MS m/z: 465.0 (M+1).
  • 38
  • [ 1001327-25-8 ]
  • [ 32333-53-2 ]
  • [ 1001326-37-9 ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; 16 Example 164-Chloro-N-[4-chloro-2-(1-methyl-1H-pyrazole-3-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide To a solution of the starting aminoketone (44 mg, 0.20 mmol) in dry pyridine (0.5 mL) was added dropwise a solution of 4-chloro-3-trifluoromethyl)benzenesulfonyl chloride (57 mg, 0.20 mmol) in dry pyridine (0.3 mL). The reaction was shaken overnight at room temperature. The reaction was separated by preparative HPLC (20 80% gradient of ACN-water) and the pure product fractions were lyophilized to provide 4-chloro-N-[4-chloro-2-(1-methyl-1H-pyrazole-3-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide as a light yellow solid: 1H-NMR (400 MHz, CDCl3): δ 7.95 (m, 1H), 7.90 (m, 1H), 8.50 (m, 4H), 7.25 (m, 2H), 7.15 (m, 1H), 3.99 (s, 3H). MS m/z: 478.0 (M+1).
  • 39
  • [ 886373-70-2 ]
  • [ 32333-53-2 ]
  • [ 1309778-84-4 ]
YieldReaction ConditionsOperation in experiment
With pyridine; dmap at 100℃; for 2h; 4-Chloro-3-(trifluoromethyl)benzenesulfonyl chloride (56 mg) was dissolved in pyridine (1 ml) and DMAP (2 mg) was added. 5-Chloro-2-(methyloxy)-3-pyridinamine (32 mg) was added and the reaction was heated to 100 °C for 2 h. The reaction was purified by HPLC using 20 - 80 % MeCN:water:TFA to give the title compound, 72 mg.LC/MS (Method E) Rt = 3.13 min, MH+ = 401 .
  • 45
  • [ 32333-53-2 ]
  • [ 6828-35-9 ]
  • [ 1382801-61-7 ]
YieldReaction ConditionsOperation in experiment
60% With pyridine at 100℃; 1 A solution of 5-chloro-2-iodoaniline (CAS 6828-35-9) (1.1 g, 4.33 mmol) and 4-chloro-3-(trifluoromethyl)benzenesulfonyl chloride (CAS 32333-53-2) (1.21 g, 4.33 mmol) in pyridine (10 ml) was stirred at 100° C. overnight. The solvent was removed in vacuo and the residue was purified by flash column chromatography on silica gel to afford Intermediate 1 as a light yellow solid (1.3 g, 60%). 1H NMR (300 MHz, CD3OD) δ 8.03 (s, 1H), 7.84-7.93 (m, 1H), 7.68-7.84 (m, 2H), 7.47 (d, J=2.34 Hz, 1H), 7.04 (dd, 1H).
  • 46
  • [ 32333-53-2 ]
  • [ 1382801-44-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: pyridine / 100 °C 2: caesium carbonate / copper(l) iodide; N,N`-dimethylethylenediamine / toluene / 110 °C / sealed tube
  • 47
  • [ 32333-53-2 ]
  • [ 1382801-49-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: pyridine / 100 °C 2: caesium carbonate / copper(l) iodide; N,N`-dimethylethylenediamine / toluene / 110 °C / sealed tube 3: 1-(Trimethylsilyl)imidazole / chloroform / 0.5 h / 20 °C 4: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 48 h / 20 °C
  • 48
  • [ 32333-53-2 ]
  • [ 1382801-56-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: pyridine / 100 °C 2: triethylamine / tetrakis(triphenylphosphine) palladium(0) / toluene / 100 °C / sealed tube
  • 49
  • [ 32333-53-2 ]
  • [ 1382801-59-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: pyridine / 100 °C 2: triethylamine / tetrakis(triphenylphosphine) palladium(0) / toluene / 100 °C / sealed tube 3: trimethylsilyl bromide / chloroform / 2 h / 70 °C
  • 50
  • [ 32333-53-2 ]
  • [ 1382801-48-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: pyridine / 100 °C 2: caesium carbonate / copper(l) iodide; N,N`-dimethylethylenediamine / toluene / 110 °C / sealed tube 3: 1-(Trimethylsilyl)imidazole / chloroform / 0.5 h / 20 °C
  • 51
  • [ 32333-53-2 ]
  • thiophene-2-sulfonic acid (3-aminopyridin-2-yl)amide [ No CAS ]
  • [ 1381969-94-3 ]
YieldReaction ConditionsOperation in experiment
18% With pyridine at 20℃; for 72h; Compound 37 N-[3-([4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2-sulfonamide To a solution Intermediate 10 (72 mg, 0.28 mmol) in pyridine (2 ml) was added 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (49 µl, 0.28 mmol) and the reaction was stirred at room temperature for 3 days, concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (50%-75% EtOAc in hexanes) to yield Compound 37 (26 mg, 18%). 1H NMR (acetone-d6) δ ppm: 8.27 (d, J = 2.1 Hz, 1H), 8.14 (dd, J = 8.4, 2.2 Hz, 1 H), 7.97 (dd, J = 7.6, 1.5 Hz, 1 H), 7.83 (dd, J = 6.4, 1.5 Hz, 1 H), 7.78 (d, J = 8.2 Hz, 1 H), 7.71 (dd, J = 5.0, 1.5 Hz, 1 H), 7.51 (dd, J = 3.7, 1.3 Hz, 1 H), 7.05 (dd, J = 5.0, 3.5 Hz, 1 H), 6.88 (dd, J = 7.8, 6.3 Hz, 1 H).
  • 52
  • [ 32333-53-2 ]
  • thiophene-2-sulfonic acid (3-amino-5-chloropyridin-2-yl)amide [ No CAS ]
  • N-[5-chloro-3-([4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% With pyridine at 100℃; for 6h; Compound 38 N-[5-chloro-3-([4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2-sulfonamide To a solution of Intermediate 11 (75 mg, 0.26 mmol) in pyridine (2 ml) was added 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (143 mg, 0.52 mmol) and the reaction was stirred at 100°C for 6 h, concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (50%-100% EtOAc in hexanes), followed by PTLC (EtOAc) to yield Compound 38 (24 mg, 17%). 1H NMR (acetone-d6) δ ppm: 8.52 (d, J = 8.5 Hz, 1 H), 8.47 (s, 1 H), 7.88 - 8.01 (m, 1 H), 7.69 (d, J = 8.2 Hz, 1 H), 7.58 (d, J = 4.7 Hz, 1 H), 7.42 - 7.51 (m, 1 H), 7.17-7.28 (m, 1 H), 6.91 - 7.01 (m, 1 H).
  • 53
  • [ 32333-53-2 ]
  • 4-amino-2-(pyridin-3-yl)isoindoline-1,3-dione [ No CAS ]
  • 3-(trifluoromethyl)-4-chloro-N-(2-(pyridin-3-yl)-1,3-dioxoisoindolin-4-yl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; for 24h;
  • 54
  • [ 29022-11-5 ]
  • [ 32333-53-2 ]
  • C20H15ClNO3Pol [ No CAS ]
  • C28H20Cl2F3N2O4PolS [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: C20H15ClNO3Pol With piperidine In N,N-dimethyl-formamide for 0.2h; Stage #2: N-(fluoren-9-ylmethoxycarbonyl)glycine With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide for 0.5h; Stage #3: 4-chloro-3-trifluoromethylbenzenesulfonyl chloride Further stages; Method a) and f) for solid phase synthesis General procedure: Fmoc-NH-O-2-Chlorotrityl resin (0.3 mmol, 1 eq) was swollen in DMF for 20 min. Fmoc-deprotection was carried out using 20% piperidine in DMF (5 ml) for 4 min and a second time for 8 min followed by washing with DMF. Fmoc-Gly-OH (1.2 mmol, 4 eq), TBTU (1.2 mmol, 4 eq) and N-methylmorpholine (2.4 mmol, 8 eq) dissolved in DMF (5 ml) were added and the mixture was shaken for 30 min. The procedure was repeated for another 30 min followed by washing the resin intensively with DMF. Fmoc-deprotection was carried out as described above followed by washing the resin with DMF. The respective sulfonylchloride (1.2 mmol, 4 eq) and triethylamine (2.4 mmol, 8 eq) dissolved in dichloromethane (5 ml) were added and the resin was shaken at room temperature for 15 hours. After washing the resin intensively with DMF, the product was cleaved from the resin using TFA (3ml) and triisopropylsilane (0.3 ml) in dichloromethane (5 ml). After 4 hours the resin was filtered off and the filtrate was evaporated. The residue was purified by semi-preparative HPLC (Varian Prostar, Phenomenex Luna C18(2) column, H2O/MeCN gradient containing 0.04% TFA).
  • 55
  • [ 32333-53-2 ]
  • 2-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)-1-phenylethan-1-one oxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrazine hydrate / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2: tert.-butylnitrite; 1H-imidazole; oxygen / 1-methyl-pyrrolidin-2-one; water / 6 h / 100 °C / Schlenk technique; Green chemistry
  • 56
  • [ 32333-53-2 ]
  • [ 1155515-90-4 ]
YieldReaction ConditionsOperation in experiment
With hydrazine hydrate In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere;
  • 57
  • [ 284462-37-9 ]
  • [ 32333-53-2 ]
  • 4-(4-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)phenoxy)-N-methylpicolinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With pyridine In dichloromethane 69 Example 69 - Preparation of 4-(4-(4-Chloro-3-(trifluoromethyl)phenylsulfonamido) phenoxy)-N-methylpicolinamide (S1/L3/C3 (APS4-67-1)) To a solution ofHB/S1 (50.0 mg, 0.206 mmol) and CH2C12 (0.5 mL) was added4-chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride (69.0 mg, 0.247 mmol; as a solution in0.5 mL CH2C12) and then pyridine (25.0 jiL, 0.309 mmol). Obtained 85.7 mg (86%) of the title compound as an off-white solid: ‘HNIVIR (400 IVIFIz, DMSO-d6) ö 10.57 (s, 1 H), 8.76 (br q, J4.4 Hz, 1 H), 8.49 (d, J=5.6 Hz, 1 H), 8.09 (d, J=2.0 Hz, 1 H), 7.97 - 8.01 (m, 1 H), 7.92 - 7.97(m, 1 H), 7.33 (d, J=2.4 Hz, 1 H), 7.14-7.22 (m, 4 H), 7.08 (dd, J=5.6, 2.7 Hz, 1 H), 2.78 (d, J4.9 Hz, 3 H); ‘9F NIVIR (376 MHz, DMSO-d6) ö -61.5 (s, 3F); LC-MS (ESI+) m/z: [M+H] Calcd for C20H,6C1F3N304S 486.1; Found 486.2 (FIGs. 41-42).
  • 58
  • [ 757251-39-1 ]
  • [ 32333-53-2 ]
  • 4-(4-(4-Chloro-3-(trifluoromethyl)phenylsulfonamido)-3-fluorophenoxy)-N-methylpicolinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With pyridine In dichloromethane 73 Example 73 - Preparation of 4-(4-(4-Chloro-3-(trifluoromethyl)phenylsulfonamido)- 3-fluorophenoxy)-N-methylpicolinamide (S2/L3/C3 (APS4-68-1)) To a solution of HB/52 (60.0 mg, 0.23 0 mmol) and CH2C12 (0.5 mL) was added 4-chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride (77.0 mg, 0.276 mmol; as a solution in0.5 mL CH2C12) and then pyridine (28.0 jiL, 0.346 mmol). Obtained 78.4 mg (68%) of the title compound as a white solid: ‘H NIVIR (400 IVIHz, DMSO-d6) ö 10.56 (s, 1H), 8.78 (br ap d, J=4.4Hz, 1H), 8.53 (d,J=5.4Hz, 1H), 8.11 (d,J1.OHz, 1H), 7.89-8.04(m, 2H), 7.41 (d,J=2.4Hz,1H), 7.35 (t, J=8.9 Hz, 1H), 7.27 (dd, J=10.9, 2.6 Hz, 1H), 7.16 (dd, J=5.5, 2.6 Hz, 1H), 7.07 (dd, J=8.7, 1.6 Hz, 1H), 2.80 (d, J4.9 Hz, 3H); ‘9F NMR (376 IVIHz, DMSO-d6) ö -61.5 (s, 3F),-118.0 (s, iF); LC-MS (ESI+) m/z: [M+H] Calcd for C20H,5C1F4N3045 504.0; Found 504.2 (FIGs. 49-50).
  • 59
  • [ 32333-53-2 ]
  • C23H33BrN2O3 [ No CAS ]
  • (1R,4aS,E)-methyl 6-bromo-9-((2-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)ethoxy)imino)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With sodium hydrogencarbonate In tetrahydrofuran at 20℃; for 4h; Inert atmosphere; 1.2. Synthesis of compound F01-35 General procedure: To a stirred solution of 4 (1.0 mmol) in THF (5 mL) was added appropriate sulfonyl chloride (1.1 mmol) and NaHCO3 (38 mmol). The reaction mixture was stirred at room temperature for 4 h under nitrogen atmosphere. Then the solvent was evaporated in vacuum. The residue was diluted with water. The whole mixture was extracted with AcOEt for three times. The combined organic layer was washed with water, sat. brine, and dried over Na2SO4. The crude product was purified by column chromatography using petroleum ether/AcOEt (10/1-8/1, v/v) as eluent to afford F01-F35.
  • 60
  • [ 32333-53-2 ]
  • C23H33BrN2O3 [ No CAS ]
  • (1R,4aS,E)-6-bromo-9-((2-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)ethoxy)imino)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / tetrahydrofuran / 4 h / 20 °C / Inert atmosphere 2: 18-crown-6 ether; potassium hydroxide / methanol / 24 h / Heating
  • 61
  • [ 32333-53-2 ]
  • C17H12ClN3O3S2 [ No CAS ]
  • 5-chloro-N-(2-(4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonamido)phenyl)benzo[d]oxazol-5-yl)thiophene-2-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine In dichloromethane at 20℃; for 18h;
  • 62
  • [ 32333-53-2 ]
  • C17H12ClN3O3S2 [ No CAS ]
  • 5-chloro-N-(4-(5-((4-chloro-3-(trifluoromethyl)phenyl)sulfonamido)benzo[d]oxazol-2-yl)phenyl)thiophene-2-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine In dichloromethane at 20℃; for 18h;
  • 63
  • [ 110-18-9 ]
  • [ 32333-53-2 ]
  • [ 55080-63-2 ]
YieldReaction ConditionsOperation in experiment
82% With calcium hydride In acetonitrile at 90℃; for 1h; Inert atmosphere; Schlenk technique; regiospecific reaction;
  • 64
  • [ 32333-53-2 ]
  • 2-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)-1-phenylethan-1-one oxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrazine hydrate / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2: 1H-imidazole; hydrazine hydrate; tert.-butylnitrite / ethanol; water / 1.5 h / 100 °C / Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry
  • 65
  • [ 32333-53-2 ]
  • [ 3963-78-8 ]
  • 4-chloro-N-(3,4-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 20℃; for 4h; Step 3. General procedure: Corresponding sulfonyl chloride (1.5 mmol)was added tothe solution of crude product 7 (255 mg,1 mmol) in dry pyridine(5 mL) and the mixture was stirred at room temperature for 4h.Then it was added to 10% aqueous HCl (50 mL) and the suspensionwasextracted with ethyl acetate. The organic phasewaswashed with brine, dried over anhydrous Na2SO4 and filtered.The residuewas purified by silica chromatography after removalof ethyl acetate to afford compounds 8a-v. 4.1.1.1. N-(3,4-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)methanesulfonamide (8a). Yellowsolid,
  • 66
  • [ 32333-53-2 ]
  • (S)-1-(1H-indol-3-yl)pent-4-en-2-amine [ No CAS ]
  • (S)-N-(1-(1H-indol-3-yl)pent-4-en-2-yl)-4-chloro-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With triethylamine In dichloromethane at 20℃; 2.2 General procedures for the synthesis of compounds 6a-6am General procedure: Compound 5 (0.2 g, 1 mmol),Triethylamine (0.48 mL, 3.5mmol) and Arylsulfonyl chloride (1.2 mmol) into a round-bottomed flask (50 mL) were resolved inCH2Cl2. The solution was stirred at rt and stirredovernight. The reaction was quenched with water and separated to theorganic lay. Organic lay were dried over Na2SO4, and concentrated invacuum. The residue waspurified by flash silica gel columnchromatography (ethyl acetate / petroleum ether, 25%) to afford 6a-6al. The yields of the derivatives (6a-6al) were 51-83%.
  • 67
  • [ 41373-37-9 ]
  • [ 32333-53-2 ]
  • 4-chloro-N-(2-phenylbenzo[d]oxazol-5-yl)-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine In dichloromethane at 20℃; for 18h; General procedure for the sulfonamide coupling reaction. General procedure: To stirring mixtures of either 4-(1,3-benzoxazol-2-yl)aniline or 2-phenyl-1,3-bezoxazol-5-amine (1 eq.) in anhydrous CH2Cl2 (5 mL) were added the respective R1-sulfonyl chlorides (1.3 eq.), followed by anhydrous pyridine (1.3 eq.). The reactions were allowed to stir at room temperature for 18 h, then chromatographed over silica (hexanes:EtOAc gradient), and concentrated. If necessary, the products were further purified by preparatory RP-HPLC (H2O:CH3CN gradient), concentrated, and lyophilized. Refer below for individual compound characterization data.
  • 68
  • [ 20934-81-0 ]
  • [ 32333-53-2 ]
  • N-(4-(benzo[d]oxazol-2-yl)phenyl)-4-chloro-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine In dichloromethane at 20℃; for 18h; General procedure for the sulfonamide coupling reaction. General procedure: To stirring mixtures of either 4-(1,3-benzoxazol-2-yl)aniline or 2-phenyl-1,3-bezoxazol-5-amine (1 eq.) in anhydrous CH2Cl2 (5 mL) were added the respective R1-sulfonyl chlorides (1.3 eq.), followed by anhydrous pyridine (1.3 eq.). The reactions were allowed to stir at room temperature for 18 h, then chromatographed over silica (hexanes:EtOAc gradient), and concentrated. If necessary, the products were further purified by preparatory RP-HPLC (H2O:CH3CN gradient), concentrated, and lyophilized. Refer below for individual compound characterization data.
  • 69
  • [ 81-64-1 ]
  • [ 32333-53-2 ]
  • 1,4-bis(4-chloro-3-(trifluoromethyl)benzenesulfonato)-9,10-anthraquinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With potassium carbonate In acetone at 60℃; 1.11; 2.11; 3.11 (11) Preparation of 1,4-bis(4-chloro-3-(trifluoromethyl)benzenesulfonate)-9,10-anthraquinone(C11): It was added 1,4-dihydroxy anthraquinone 0.5g (2mmol) in a glass flask,Excess 4-Chloro-3-trifluoromethylbenzenesulfonyl chloride 3.9 g,Anhydrous potassium carbonate 0.5g,Then add 20 mL of anhydrous acetone,The reaction is refluxed in an oil bath at 60 ° C,TLC monitors the response throughout the process,After the reaction,Add appropriate amount of ice water to quench the reaction.Filtered to light yellow crude product,Purified by silica gel column chromatography.Eluent (dichloromethane: petroleum ether = 1:2) to give a pale yellow target compound.The yield was 63%.
  • 70
  • [ 116797-02-5 ]
  • [ 32333-53-2 ]
  • 1'-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)-4-methyl-1,4'-bipiperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;
  • 71
  • [ 106-52-5 ]
  • [ 32333-53-2 ]
  • N-(but-3-en-1-yl)-4-chloro-N-methyl-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: N-methyl-4-hydroxypiperidine With alizarin yellow R In acetonitrile for 0.333333h; Inert atmosphere; Stage #2: 4-chloro-3-trifluoromethylbenzenesulfonyl chloride In acetonitrile at 20℃; for 24h; Irradiation; Inert atmosphere; 2 Example 2: Synthesis of N-(but-3-en-1-yl)-4-chloro-N-methyl-3-(trifluoromethyl)benzenesulfonamide Add 20 mg of calcium hydride as a desiccant to a dry 10 ml reaction tube. Nitrogen is introduced to create an oxygen-free environment for the reaction system. Take 1-methylpiperidin-4-ol (138 mg, 1.2 mmol), Alizarin Yellow R (5 mol%) was dissolved in 1.5 ml of acetonitrile and syringed into the reaction tube. After stirring for 20 minutes, p-chlorotrifluoromethylbenzenesulfonyl chloride (279 mg, 1.0 mmol) was dissolved in 1.5 ml of acetonitrile and syringe was introduced into the reaction system. The reaction was carried out for 24 hours under the illumination of a normal temperature 30w LED lamp, and the light was removed. (20ml) quenched with saturated NH4Cl solution, and (20ml × 3 times) and extracted with ethyl acetate, the organic phase retained and washed once with saturated aqueous NaCl solution. The solvent was distilled off under reduced pressure, flash column chromatography to give 252 mg of product, 77% yield.
77% With calcium hydride; alizarin yellow R In acetonitrile at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; Green chemistry;
  • 72
  • [ 32333-53-2 ]
  • 1-(5,5-bis(4-fluorophenyl)pentyl)-4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Inert atmosphere 2: sodium carbonate; potassium iodide / acetonitrile / 12 h / Inert atmosphere; Reflux
  • 73
  • [ 110-85-0 ]
  • [ 32333-53-2 ]
  • 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere; 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine (45). DIPEA (0.194 g, 1.5 mmol) was added to a solution of substituted phenyl sulphonyl chloride 43 (0.20 g, 0.75 mmol) and piperazine 44 (0.19 g, 2.15 mmol) in dichloromethane (2 mL) and stirred overnight at room temperature. The reaction was quenched with water (10 mL), extracted with dichloromethane (3 × 10 mL). The combined organic portion was dried over Na2SO4 and filtered. The organic solvent was removed under reduced pressure, and formed residue was purified with column chromatography using methanol / dichloromethane (1:99 to 1:24) to obtain compound 45 (0.05 g, 41%) as a white solid. 1H NMR (400 MHz, CDCl3) δH 2.88-2.98 (m, 4H), 2.98-3.13 (m, 5H), 7.70 (d, 1H, J = 8.31 Hz), 7.86 (dd, 1H, J = 8.31, 1.96 Hz), 8.05 (d, 1H, J = 1.83 Hz).
  • 74
  • [ 32333-53-2 ]
  • C15H14N4O [ No CAS ]
  • 4-(5-(4-chloro-3-(trifluoromethyl)benzenesulfonamido)-1H-indol-1-yl)-N-methylpyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% Stage #1: C15H14N4O With triethylamine In tetrahydrofuran at 0 - 20℃; for 0.25h; Inert atmosphere; Stage #2: 4-chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride In tetrahydrofuran at 0 - 20℃; 4.9. Synthesis of the target sulfonamide derivatives 1p-t General procedure: A solution of compound 5 (100 mg, 0.38 mmol) in anhydrousTHF (2 mL) was cooled to 0 C and stirred under N2 (g). TEA(0.95 mmol, 33 mL) was added thereto, and the reaction mixture was left under stirring at room temperature for 15 min. A sulfonylchloride derivative (0.76 mmol) dissolved in THF (1 mL) was addeddropwise to the mixture at 0 C. The reaction was stirred at roomtemperature for 4e12 h. Upon reaction completion, the mixturewas dried by rotary evaporator. The crude compound was thenextracted by ethyl acetate (25 mL) and distilled water (25 mL). Theorganic layer was collected, dried over Na2SO4, and filtered. Thefiltrate was dried over rotary evaporator. The compound wasfurther purified using flash column chromatography.
With triethylamine
  • 75
  • N-((5-methylfuran-2-yl)methyl)prop-2-en-1-amine [ No CAS ]
  • [ 32333-53-2 ]
  • (3aRS,6RS,7aRS)-2-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}-6-methyl-1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindole [ No CAS ]
  • N-allyl-4-chloro-N-[(5-methylfuran-2-yl)methyl]-3-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 40% 2: 20% With sodium carbonate In water at 100℃; for 3h; diastereoselective reaction; 2.3.1. 2-(Arylsulfonyl)-1,2,3,6,7,7a-hexahydro-3a,6-epoxyisoindoles (2 and 4), 2-[(4-methylphenyl)sulfonyl]-1,3,4,7,8,8a-hexahydro-2H-4a,7-epoxyisoquinoline (7a) and N-substituted N-arylsulfonamides (3, 5, 6, 8 and 9); general procedure General procedure: The corresponding arylsulfonyl chloride (43 mmol) was added to the corresponding amine 1 (36 mmol) in water (50 mL) in the presence of Na2CO3 (43 mmol). The resulting reaction mixture was refluxed for 3 h, the formed powder was filtered off and rinsed with hexane. When it was needed, the resulting reaction mixture extracted with ethyl acetate (3x50 mL). The organic layers were dried with anhydrous MgSO4. The solution was filtered and concentrated. The resulting dark brown oils were triturated with hexane and the obtained solid was recrystallized from a hexane-EtOAc mixture or in rare cases from hexane with a dropwise adding of EtOH. The formed crystals were filtered, washed with hexane (3 5 mL) and dried in air to give the title arylsulfonyl-3a,6-epoxyisoindoles (2, 4) as white powders. In cases when the separation of “cyclic” and “non-cyclic” products was needed or only “non-cyclic” products were formed, column chromatography was used (SiO2, 23x1.6 cm, eluent: hexane-ethyl acetate, gradient from 20:1 to 5:1). The physicochemical characteristics of compounds 2a, b, n have been published previously [28].
  • 76
  • C12H18N6O4 [ No CAS ]
  • [ 32333-53-2 ]
  • C19H20ClF3N6O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: C12H18N6O4 With triethylamine In dichloromethane; N,N-dimethyl-formamide at 0℃; for 1h; Stage #2: 4-chloro-3-trifluoromethylbenzenesulfonyl chloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 4h;
  • 77
  • [ 32333-53-2 ]
  • C10H8ClF3N4O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0 - 20 °C 2: trimethylsilylazide; water; silver carbonate / dimethyl sulfoxide / 2 h / 80 °C
  • 78
  • [ 32333-53-2 ]
  • 3-azido-1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)-3-fluoroazetidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: trimethylsilylazide; water; silver carbonate / dimethyl sulfoxide / 2 h / 80 °C 3.1: [bis(acetoxy)iodo]benzene / dichloromethane / 25 °C / Schlenk technique 3.2: 0.08 h / Schlenk technique
  • 79
  • [ 32333-53-2 ]
  • [ 2450-71-7 ]
  • C10H7ClF3NO2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 0 - 20℃;
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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Aryls

Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1866403-21-5

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4-Chloro-3-(trifluoromethyl)benzene-1-sulfinic chloride

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Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Sulfonyl Chlorides

Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 875167-01-4

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3-Chloro-5-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chlorides

Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1866403-21-5

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4-Chloro-3-(trifluoromethyl)benzene-1-sulfinic chloride

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Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Trifluoromethyls

Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1214346-10-7

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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Chemical Structure| 1866403-21-5

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4-Chloro-3-(trifluoromethyl)benzene-1-sulfinic chloride

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Chemical Structure| 132481-85-7

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3-Chloro-4-(trifluoromethyl)benzene-1-sulfonyl chloride

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2-Chloro-3-(trifluoromethyl)benzene-1-sulfonyl chloride

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