Structure of 383-31-3
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CAS No. : | 383-31-3 |
Formula : | C8H10FNO2S |
M.W : | 203.23 |
SMILES Code : | O=S(C1=CC=C(F)C=C1)(N(C)C)=O |
MDL No. : | MFCD01211990 |
InChI Key : | WURMPFYVFDHATI-UHFFFAOYSA-N |
Pubchem ID : | 799301 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.76 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.45 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.58 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.66 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.62 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.22 |
Solubility | 1.22 mg/ml ; 0.00598 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.02 |
Solubility | 1.96 mg/ml ; 0.00962 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.72 |
Solubility | 0.389 mg/ml ; 0.00191 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 |
-6.51 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 |
0.0 |
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) |
1.97 |
* 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 |
---|---|---|
35% | 2) To <strong>[383-31-3]4-fluoro-1-(N,N-dimethylaminosulfonyl)benzene</strong> (2.03 g, 10.0 mmol) were added diisopropylethylamine (2.26 mL, 13.0 mmol) and 1,2-diamino-2-methylpropane (3.14 mL, 30.0 mmol), and the mixture was heated with stirring at 170 DEG C for 10 hours. To the mixture was added a 2 mol/L aqueous sodium hydroxide solution, and the aqueous layer was extracted with chloroform. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography. (Chromatorex (registered trademark) NH, Fuji Silysia, hexane/chloroform = 1/1) to obtain the title compound (956 mg, 3.52 mmol).yield: 35%<1>H NMR (CDCl3) delta (ppm) : 7.55 (2H, d, J = 9.2 Hz), 6.64 (2H, d, J = 9.2 Hz), 4.83 (1H, t, J = 5.7 Hz), 3.00 (2H, d, J = 5.7 Hz), 2.66 (6H, s), 1.21 (6H, s).APCIMS (m/z): 272 (M + H)<+> |
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 |
---|---|---|
With potassium fluoride; potassium carbonate; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dimethyl sulfoxide; N,N-dimethyl-formamide; | EXAMPLE 24 4-[4-(2,4 -Diamino-6-methyl-5-pyrimidinyl)-1-piperazinyl]-N,N-dimethylbenzenesulfonamide A mixture of 10.4 g (0.05 mole) of 6-methyl-5-(1-piperazinyl)-2,4-pyrimidinediamine triacetate, 10.1 g (0.05 mole) of <strong>[383-31-3]4-fluoro-N,N-dimethylbenzenesulfonamide</strong>, 6.4 g (0.055 mole) of anhydrous potassium fluoride, and 27.6 g (0.2 mole) of powdered potassium carbonate in 100 ml of dimethylsulfoxide was heated at 120 C. for four hours. The reaction mixture was cooled and poured into 300 ml of ice water. The solid was collected and washed with ml of water. Recystallization from N,N-dimethylformamide gave 6.5 g of the product as an off-white solid, mp 301-304 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In dimethyl sulfoxide; at 130℃; for 24h; | (2) In 600 ml of DMSO were suspended 25 g of (S)-(-)-3-(tert-butoxycarbonylamino)pyrrolidine, 47.9 g of 4-fluoro-N,N-dimethyl-benzenesulfonamide and 139 g of potassium carbonate, and the mixture was stirred at 130C for 1 day. To the reaction mixture were added water and ethyl acetate, the resulting mixture was stirred and the liquids were separated. The organic layer was washed with water, and then dried, and the solvent was evaporated. The residue was dissolved in chloroform, NH silica gel was added thereto and the mixture was allowed to stand for a while, and silica gel was filtered off. The silica gel was further washed with ethyl acetate. The filtrate and the washed solution were combined, and the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=80:20? 67:33) to obtain 8.39 g of tert-butyl [(S)-1-(4-dimethylsulfamoylphenyl)-pyrrolidin-3-yl]carbamate. MS·APCI (m/z): 370 [M+H] + |
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 |
---|---|---|
82% | A solution of 4-fluoro-Lambda/,Lambda/-dimethylbenzenesulfonamide (1.80 g; 8.86 mmol) in cone, sulfuric acid (7 ml; 130 mmol) was treated with Lambda/-bromosuccinimide (1 730 mg; 9.74 mmol) and stirred at RT for 3 h. The reaction mixture was carefully poured on crushed ice, extracted with AcOEt and the organic phase was washed with a 0.1 N solution of NaOH in water twice, then with brine twice. The organic phase was dried on MgSO4, filtered and concentrated under reduced pressure to give the title compound as a white solid (2.04 g, 82%).1H NMR (300MHz, DMSO-d6) delta [ppm] 8.04 (1 H, dd, J= 6.5 Hz, J= 2.2 Hz), 7.83 (1 H, ddd, J= 8.7 Hz, J= 4.6 Hz, J= 2.3 Hz), 7.66 (1 H, t, J= 8.7 Hz), 2.65 (6H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; | Preparation of ethyl 4-{4-f(dimethylamino)sulfonyllphenoxy}-2-methyl-2H- indazole-6-carboxylate (l-1f-35):(l-1f-35)The title compound was prepared by heating a mixture of ethyl 4- hydroxy-2-methyl-2H-indazole-6-carboxylate (l-1e-3, 70mg, 0.32 mmol), 4- fluoro-N,N-dimethylbenzenesulfonamide (71.1 mg, 0.35 mmol), and cesium carbonate (114 mg, 0.35 mmol) in N,N-dimethylformamide (0.795 ml_) at 1000C overnight. The reaction mixture was then cooled, concentrated, dissolved in water, and extracted three times with dichloromethane. The combined organic layers were concentrated and the crude product was purified by flash chromatography eluting with a 20-65% gradient of ethyl acetate in heptane to afford ethyl 4-{4-[(dimethylamino)sulfonyl]phenoxy}-2- methyl-2H-indazole-6-carboxylate (l-1f-35, 68 mg, 53%).1H NMR (400 MHz, CHLOROFORM-d) ppm 1.39 (t, J=7.13 Hz, 3H), 2.72 (s, 6 H), 4.22 (s, 3 H), 4.39 (q, 2 H), 7.13 (d, J=8.99 Hz, 2 H), 7.31 (d, J=1.17 Hz, 1 H), 7.69 - 7.78 (m, 3 H), 8.35 (s, 1 H). MS (M+1 ) 403.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With sodium thiomethoxide; In N,N-dimethyl-formamide; at 170℃; for 16h;Sealed tube; | [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). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | General procedure: An oven-dried Schlenk tube equipped with a magnetic stir bar was charged with formamide 1 (2.0 mmol), KO-t-Bu (2.0 mmol) and CH3CN (2.0 mL). The mixture was stirred at 50 C for 30 min and then a CH3CN (2.0 mL) solution containing sodium sulfinates 2 (0.5 mmol) and NIS (1.0 mmol) was slowly added dropwise. The resulting solution stirred at 50 C for 12 h under air. The mixture was then cooled to room temperature, diluted with 30 mL of H2O, and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel to give the products. |
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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