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Structure of 349-88-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 349-88-2 |
Formula : | C6H4ClFO2S |
M.W : | 194.61 |
SMILES Code : | O=S(C1=CC=C(F)C=C1)(Cl)=O |
MDL No. : | MFCD00007438 |
InChI Key : | BFXHJFKKRGVUMU-UHFFFAOYSA-N |
Pubchem ID : | 9588 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 39.48 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.52 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.66 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.04 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.67 |
Solubility | 0.417 mg/ml ; 0.00214 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.56 |
Solubility | 0.535 mg/ml ; 0.00275 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.22 |
Solubility | 0.117 mg/ml ; 0.000601 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.04 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.77 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; In tetrahydrofuran; water; at 20℃; for 0.333333h; | (1) 4-Fluoro-1-(N,N-dimethylaminosulfonyl)benzene To a solution of 4-fluorobenzenesulfonyl chloride (1.95 g, 10.0 mmol) in THF (40 mL) were added triethylamine (2.09 mL, 15.0 mmol) and 50% aqueous dimethylamine solution (1.26 mL, 14.0 mmol) at room temperature, and the solution was stirred at the same temperature for 20 minutes. The reaction mixture was diluted with ethyl acetate, and washed with water. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain 4-fluoro-1-(N,N-dimethylaminosulfonyl)benzene (2.03 g, 10.0 mmol).yield: quantitative |
100% | In methanol; dichloromethane; at 20℃; for 0.0833333h; | [00728] A mixture of 4-fluorobenzene-1 -sulfonyl chloride (2.0 g, 10.3 mmol), HNMe2 (2.0M in MeOH; 1 1 .0 mL, 22.0 mmol) and DCM (1 1 .0 mL) was stirred at rt for 5 min. DCM (30 mL) was added. The organic phase was washed with 1 M HCI (30 mL) and brine (30 mL), dried over MgSCv and filtered. The solvent was removed under reduced pressure to afford 4-fluoro-/V,/V- dimethylbenzenesulfonamide as a white solid (2.12 g, quant.). A mixture of 4-fluoro-/V,/V- dimethylbenzenesulfonamide (1 .50 g, 7.39 mmol), NaSMe (2.08 g, 29.7 mmol) and DMF (9.0 mL) was stirred at 170 C in a sealed tube for 16 h. After cooling to rt, 1 M NaOH (40 mL) was added. The aqueous phase was washed with Et20 (2 chi 40 mL), acidified to pH <2 with 2 M HCI and then extracted with Et20 (3 chi 40 mL). The combined organic phase was dried over MgSCv and filtered. The solvent was removed under reduced pressure to afford 4-mercapto-/V,/V- dimethylbenzenesulfonamide as an orange oil (503 mg, 31 %). H NMR (500 MHz, CDCI3) delta 7.67 - 7.58 (m, 2H), 7.43 - 7.35 (m, 2H), 3.67 (s, 1 H), 2.71 (s, 6H). |
86% | In tetrahydrofuran; at 0℃; for 0.5h; | A cooled (0 0C) solution of 4-fluorobenzenesulfonyl chloride (2.00 g; 10.3 mmol) in THF (40 ml) is treated with a 2 M solution of dimethylamine in THF (1 1.3 ml; 22.6 mmol) and stirred at 0 0C for 30 minutes. The solvents were removed under reduced pressure, the residue taken up in EtOAc, the organic phase was washed with a saturated solution of NH4CI twice and with water. The organic phase was dried on MgSO4, filtered and the solvent removed under reduced pressure to afford the title compound (1.80 g, 86%). |
In tetrahydrofuran; water; at 0 - 20℃; for 24h; | (1) A solution of 50 g of 4-fluorobenzenesulfonyl chloride in 250 ml of THF was cooled to 0C, and then, 100 ml of an aqueous 50% dimethylamine solution was added dropwise thereto, and the mixture was stirred at room temperature for 1 day. To the reaction mixture were added water and ethyl acetate, the mixture was stirred and then the liquids were separated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and dried, the solvent was evaporated, and diisopropyl ether and hexane were added to the residue. Then, the precipitates were collected by filtration and washed with hexane to obtain 49.9 g of 4-fluoro-N,N-dimethyl-benzenesulfonamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; ethyl acetate; | 4-Fluoro-N,N-dimethylbenzenesulfonamide A solution of 38.9 g (0.20 mole) of 4-fluorobenzenesulfonylchloride in 20 ml of methylene chloride was added slowly to 300 ml of a 40% aqueous dimethylamine solution during 0.5 hour period. The reaction was exothermic. After the reaction mixture was cooled a yellow solid was precipitated. The solid was collected, dissolved in 300 ml of ethyl acetate, and dried over magnesium sulfate. The solution was concentrated to 100 ml and a light yellow crystal formed. The crystal was collected and air-dried to afford 39 g of the product, mp 40-43 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With triethylamine; In tetrahydrofuran; water; | 66-1) 1-[2-(4-Fluorobenzenesulfonylamino)ethyl]-4-(t-butoxycarbonyl)piperazine The 1-(2-aminoethyl)-4-(t-butoxycarbonyl)piperazine (2.01 g) obtained in Example 58 and 4-fluorobenzene sulfonylchloride (2.05 g) were dissolved in tetrahydrofuran (20 ml), and triethylamine (2.4 ml) was added thereto, and the mixture was stirred overnight at room temperature. Water (50 ml) was added to the reaction mixture which was then extracted with ethyl acetate, and the organic layer was washed with water, dried, and evaporated. The residue was purified by Cromatorex NH silica gel column chromatography (hexane/ethyl acetate system), whereby the title compound (2.61g, 77percent) was obtained as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example II-14 N-t-butoxycarbonyl-DL-4-[(4-fluorophenyl)sulfonylamino]-phenylalanine In the same manner as in Example II-(11-2) and Example II-(11-3) except for using N-t-butoxycarbonyl-DL-4-aminophenylalanine ethyl ester in place of N-t-butoxycarbonyl-L-4-aminophenylalanine ethyl ester and using 4-fluorobenzenesulfonyl chloride in place of benzenesulfonyl chloride, the reactions were carried out to obtain the title compound (overall yeield-quantitative) as white solid. 1H-NMR (CDCl3) delta; 7.78-7.71 (m, 2H), 7.21 (s, 1H), 7.13-6.91 (m, 6H), 5.03-4.88 (m, 1H), 4.67-4.49 (m, 1H), 3.19-2.89 (m, 2H), 1.42 (s, 9H). CI-MS (m/z); 383 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 125 3-(4-Fluoro-benzenesulfonylamino)-4-methoxy-N-phenyl-benzamide Prepared according to the procedure described for Example 121 using 4-fluorobenzenesulfonyl chloride (2.14 g 10 mmol) and 3-amino-4-methoxy-N-phenyl-benzamide (2.43 g, 10.0 mmol) to afford the product (3.522 g); m.p. 209-211 C. Calculated for C20H17FN2O4S: C, 59.99; H, 4.28; N, 7.00. Found: C, 59.96; H, 4.24; N, 6.87. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; | EXAMPLE 8 To a suspension of <strong>[214147-48-5]1-acetyl-4-aminopiperidine hydrochloride</strong> (715 mg) in dichloromethane (7 ml) were added diisopropylethylamine (1.83 ml) and a solution of 4-fluorobenzenesulfonyl chloride (0.83 mg) in dichloromethane (2 ml) at ambient temperature. After stirring for 6.5 hours, the reaction mixture was diluted with dichloromethane and washed with water, saturated aqueous sodium hydrogen carbonate, and brine. After drying with magnesium sulfate, the solvents were removed under reduced pressure. A residue was purified by column chromatography (silica gel 50 ml, dichloromethane:methanol=50:1 to 20:1). After rinse with diisopropyl ether, N-(1-acetylpiperidin-4-yl)-4-fluorobenzenesulfonamide (859 mg) was obtained. NMR (DMSO-d6, delta): 1.21 (2H, m), 1.54 (2H, m), 1.94 (3H, s), 2.66 (1H, br t, J=10.8 Hz), 3.02 (1H, dt, J=2.9, 12.0 Hz), 3.22 (1H, m), 3.64 (1H, br d, J=14.0 Hz), 4.05 (1H, br d, J=13.2 Hz), 7.44 (2H, t, J=8.9 Hz), 7.8-8.0 (3H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With dmap; In tetrahydrofuran; at 20℃; | Preparation of 4-fluoro-N,N-dimethyl-benzenesulfonamide A solution of 4-fluorobenzenesulfonyl chloride (1.95 g, 10 mmol) and dimethylamine hydrochloric acid salt (978 mg, 12 mmol) in tetrahydrofuran (10 mL) was added to a solution of 4-dimethylaminopyridine (3.05 g, 25 mmol) in tetrahydrofuran (10 mL) dropwise at room temperature. The resulting mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was purified by flash column (elution with 20% ethyl acetate in petroleum ether) to afford 4-fluoro-N,N-dimethyl-benzenesulfonamide (1.02 g, 50%) as a white solid. The following sulfonamides were prepared in an analogous manner as described for 4-fluoro-N,N-dimethyl-benzenesulfonamide by the reaction of 4-fluorobenzenesulfonyl chloride with commercially available amines. |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 1h; | Dimethylamine hydrochloride (1.27g) was added to a solution OF 4-FLUORO- benzenesulphonyl chloride (3. 0G) and N, N-diisopropylethylamine (5. 37ML) in dichloromethane (30ML), the mixture was stirred at RT for lh, diluted with water, extracted with dichloromethane, dried and evaporated under reduced, yield 3.0g |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In pyridine; | N-{6-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-1H-indol-4-yl}-4-fluoro-benzenesulfonamide. Substituting N-(6-bromo-1H-indol-4-yl)-4-fluoro-benzenesulfonamide (prepared by treatment of <strong>[350800-81-6]6-bromo-1H-indol-4-ylamine</strong> with 4-fluoro-benzenesulfonyl chloride in pyridine) for 6-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one. MP=295-297 C, (M+H)+=492. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; | N-{6-[7-(2,2-Dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-1H-indol-4-yl}-4-fluoro-benzenesulfonamide. Substituting N-(6-bromo-1H-indol-4-yl)-4-fluoro-benzenesulfonamide (prepared by treatment of <strong>[350800-81-6]6-bromo-1H-indol-4-ylamine</strong> with 4-fluoro-benzenesulfonyl chloride in pyridine) for 6-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one. MP=295-297 C, (M+H)+=492. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With pyridine; at 80℃; for 3.0h; | 7-Bromo-1,2,3,4-tetrahydroquinoline (0.60 g, 2.8 mmol) was stirred with 4- fluorophenylsulphonyl chloride (1.65 g, 8.49 mmol) in pyridine (5 mL) at 80 C for 3 h. The mixture was cooled, concentrated, and the residue was chromatagraphed (EtOAc/Hexanes on Si02) to give 845 mg of a brown solid (81 %) of compound 43. C15H13BrFN02S 368.98, found 394.0 [M + Na]+ and 367.8 [M - H] 1H NMR (500 MHz, CDCW) delta 1.58 - 1.67 (m, 2 H) 2.41 (t, 7=6.71 Hz, 2 H) 3.72 - 3.82 (m, 2 H) 6.89 (d, 7=8.30 Hz, 1 H) 7.08 - 7.17 (m, 2 H) 7.18 - 7.24 (m, 1 H) 7.59 - 7.68 (m, 2 H) 7.92 - 8.01 (m, 1 H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sodium hydroxide; In tetrahydrofuran; at 0 - 20℃; for 18h; | 4-Fluorobenzene-1 -sulfonyl chloride (2.14 g, 11.00 mmol, 1.00 equiv) was added into a solution of <strong>[2133-34-8](2S)-azetidine-2-carboxylic acid</strong> (1 g, 9.89 mmol, 1.10 equiv) in saturated aqueous sodium hydroxide (6 mL)/tetrahydrofuran (6 mL) at 0C. The resulting mixture was stirred for 18 h at room temperature. The mixture was extracted with ether. The pH value of the aqueous solution was adjusted to 3 with 2 M hydrogen chloride. The resulting mixture was extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in the title compound (1.7 g, 60%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With pyridine; at 0℃; for 2h;Inert atmosphere; | General procedure: To an ice-cooled solution of the amine (20mmol) in pyridine (8mL) was slowly added the corresponding sulfonyl chloride (30mmol) in pyridine (6mL). The mixture was stirred at 0°C for 2h and allowed to reach room temperature. Water was added (100mL) and the solid was collected and recrystallized from MeOH:CH2Cl2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With pyridine; In dichloromethane; at 20℃; for 4h; | To a solution of <strong>[105655-01-4]6-bromo-3,4-dihydro-2H-benzo[b][1,4]oxazine</strong> (350 mg, 1.6 mmol) in dichloromethane (5 mL) was added pyridine (0.53 mL, 6.5 mmol) followed by 4-fluorobenzenesulfonyl chloride (0.38 g, 2.0 mmol). The reaction mixture was stirred at ambient temperature for 4 hours. Then, the reaction mixture was concentrated in vacuo to provide a residue, which was redissolved in ethyl acetate, washed with 1M hydrogen chloride, brine, dried with sodium sulfate, filtered and concentrated in vacuo to provide the crude product. The crude product was purified by column chromatography (eluting with a gradient of 0-30% ethyl acetate in hexanes) to provide the title compound (0.49 g, 81% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.8% | With triethylamine; In dichloromethane; at 25℃; for 4h; | General procedure: To a mechanically stirred suspension of suspension of 1 (0.21 g, 0.53 mmol) in 30 ml CH2Cl2 were added triethylamine (0.5 ml) and aromatic sulfonyl chloride (0.53 mmol) at 25 C for 4 h. The reaction process was detected by TLC method. Then, antagonized by dilute sodium hydroxide, extracted, and washed with ether and water, evaporated under vacuum. Finally, the mixture was recrys-tallizated from ethyl acetate , providing a total product yield of 65.4%-88.6 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triethylamine; In acetonitrile; at 25℃; for 24h; | (1) 1 mmol of latinosyl N, N-dimethylamino-3-methylindole shown in Formula 1, 1.5 mmol of 4-fluorobenzenesulfonyl chloride as shown in Formula 2g was added to a 50 mL flask, Add 10mL of CH3CN to completely dissolve, slowly add 1.5mmol of Et3N, The reaction was stirred at 25 C for 24h to obtain a reaction solution; the reaction formula is as follows: (2) The reaction solution was concentrated under reduced pressure, CH2Cl2 and water were added, and the organic phases were combined. It was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was concentrated and evaporated to dryness, and then separated by silica gel column chromatography to obtain N, N-dimethylsulfonamide derivatives as shown in Formula 3g. |
82% | With triethylamine; In acetonitrile; at 25℃; for 24h; | General procedure: To a solution of gramine (1, 1.0mmol) and arylsulfonyl chloride (2, 1.5mmol) in dryCH3CN (10ml) at 25 C, a solution of Et3N (1.5mmol) in dry CH3CN (5ml) was addeddrop wise for 10min [20-24]. After reaction for 24 h, the reaction solution was concentratedunder reduced pressure to give crude product. The crude product was dissolvedin CH2Cl2 (15ml) and diluted with water (15ml) and extracted with CH2Cl2 (30ml 3). Subsequently, the combined organic phase was washed by saturated aq. brine(30ml), dried over anhydrous Na2SO4, concentrated in vacuo, and purified by silica gelcolumn chromatography to obtain the target compounds in 76%-98% yields. The datafor 3a-o are shown as follows. |
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