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Structure of 594-44-5
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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. : | 594-44-5 |
Formula : | C2H5ClO2S |
M.W : | 128.58 |
SMILES Code : | CCS(=O)(Cl)=O |
MDL No. : | MFCD00007460 |
InChI Key : | FRYHCSODNHYDPU-UHFFFAOYSA-N |
Pubchem ID : | 11667 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H310-H314-H330 |
Precautionary Statements: | P260-P280-P284-P302+P350-P305+P351+P338-P310 |
Class: | 6.1(8) |
UN#: | 2927 |
Packing Group: | Ⅱ |
Num. heavy atoms | 6 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 25.49 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.52 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.02 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.75 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.66 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.08 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.04 |
Solubility | 11.6 mg/ml ; 0.0904 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.22 |
Solubility | 7.7 mg/ml ; 0.0599 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.17 |
Solubility | 8.61 mg/ml ; 0.067 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) |
No |
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 |
-6.55 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 |
2.0 |
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) |
2.17 |
* 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 |
---|---|---|
73% | Step 1: Ethylsulphonamide : The title compound was prepared using the same procedure as described in Example 12, Step 1, replacing isopropylsulphonyl chloride with ethylsulphonyl chloride. The compound was purified by trituration with hexane to give the product (6.17g, 73%) as a colourless solid. mp 53-56C. 1H NMR (360MHz, D6-DMSO) delta 1.22 (3H, t, J = 7.4Hz), 2.95 (2H, q, J = 7.4Hz), 6.69 (2H, brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; at 0℃; for 0.25h; | 3-(2-Hydroxy-5-methylphenyl)-3-phenylpropanol (4.84 g, 20 mmol) is suspended in 20 ml of dichloromethane. Triethylamine (7.0 ml, 50 mmol) is added and the resulting clear solution is cooled to 0 0C. After the slow addition of ethanesulfonyl chloride (4.2 ml, 44 mmol) the mixture is stirred for 15 minutes at 0 0C. tert-Butyl methyl ether (MTBE, 100 ml) is added. The mixture is washed with 1 mol/l solution of hydrochloric acid (2 x 50 ml), 5 percent solution of sodium hydrogen carbonate (50 EPO <DP n="21"/>ml) and brine (50 ml). The organic phase is dried over anhydrous magnesium sulfate, filtrated and evaporated in vacuo to give the product as a brown oil in quantitative yield (8.5 g).1H NMR (300 MHz, CDCI3): delta [ppm] = 1.37 (3H, t, J = 7.5 Hz, CH2CH3), 1.53 (3H, t, J = 7.5 Hz, CH2CH3), 2.32 (3H1 s, CH3), 2.43 - 2.53 (2H, m, CH2), 3.07 (2H, q, J = 7.5 Hz, CH2CH3), 3.28 (2H, dq, J = 7.5, 1.4 Hz, CH2CH3), 4.22 - 4.37 (2H, m, CH2), 4.60 (1 H, t, J = 7.9 Hz1 CH), 7.02 - 7.07 (1 H, m, 1 H-Ar), 7.09 - 7.13 (1 H, m, 1 H-Ar), 7.19 - 7.35 (6H, m, 1 H-Ar, Ph). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; | Example 134 3-Ethanesulfonylamino-4-methoxy-N-phenyl-benzamide Prepared according to the procedure described for Example 121 using ethanesulfonyl chloride (1.5 mL, 15.8 mmol), 3-amino-4-methoxy-N-phenyl-benzamide (2.43 g. 10 mmol) and pyridine (25 mL) to afford the product (3.023 g); m.p. 175-177 C. after trituration in hexanes/ethyl acetate (1:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In a dry round bottom flask was placed <strong>[240401-22-3]4-cyanopiperidinium chloride</strong> (13, 5g, 45.4 mmol) dichloromethane (150ml) and triethylamine (18.98ml, 136 mmol). To the reaction was added dropwise ethanesulfonyl chloride (4.56 ml, 45.4 mmol) and the solution stirred 1 hour and quenched with water (100 ml). The mixture was extracted with dichloromethane (3x 50 ml) and the combined organic <n="55"/>fractions dried (MgSO4), filtered, and the solvent evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexanes to give 1- (ethylsulfonyl)pirhoeridine-4-carbonitrile (14) as a white solid. MS 203 (M+l) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With pyridine; at 0℃; for 1h; | Step 1: (4-Bromo-2-fluorophenyl)methanamine (924 mg, 4.53 mmol) was dissolved in No.64 pyridine and No.266 ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at 0° C. The mixture was stirred for 1 h at 0° C. Then, the mixture was quenched with 1N No.85 HCl and extracted with ethyl acetate. Drying over magnesium sulfate and evaporation of the ethyl acetate and purified by column chromatography gave No.276 N-(4-bromo-2-fluorobenzyl)-ethanesulfonamide in pure form (1.06 g, 79percent).[0518]Step 2: To a solution of No.276 N-(4-bromo-2-fluorobenzyl)ethanesulfonamide (305 mg, 1.03 mmol) in No.56 dimethylformamide, No.82 Manganese (113 mg, 2.06 mmol), No.83 (2,2?-Bipyridine)nickel(II)-dibromide (27 mg, 0.07 mmol), No.81 ethyl 2-chloropropanoate (0.17 mL, 1.34 mmol) was added. It was followed by addition of No.84 trifluoroacetic acid (0.002 mL, 0.028 mmol). The mixture was stirred for 24 h at 65° C. The reaction mixture was quenched by concentrated HCl (7 drops). Then it was extracted with diethyl ether, dried over magnesium sulfate, the solvent was evaporated in vacuo. It was purified by column chromatography to obtain No.278 ethyl 2-(4-(ethylsulfonamidomethyl)-3-fluorophenyl)propanoate in pure form (65 mg, 20percent).[0519]Step 3: To a solution of No.278 ethyl 2-(4-(ethylsulfonamidomethyl)-3-fluorophenyl)propanoate (60 mg, 0.189 mmol) in No.27 tetrahydrofuran and water co-solvent, No.88 sodium hydroxide (19 mg) was added at room temperature. The mixture was stirred for overnight and extracted with ethyl acetate, dried over magnesium sulfate, the solvent was evaporated in vacuo. It was purified by column chromatography to give No.280 2-(4-(ethylsulfonamidomethyl)-3-fluorophenyl)propanoic acid (55 mg).[0520]Step 4: No.280 2-(4-(Ethylsulfonamidomethyl)-3-fluorophenyl)propanoic acid (60 mg, 0.207 mmol) and No.36 (2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methanamine (61 mg, 0.228 mmol) was dissolved and mixed in No.32 1,4-dioxane, followed by addition of No.34 N-hydroxybenzotriazole (42 mg, 0.311 mmol) and No.33 N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide (60 mg, 0.311 mmol) and No.35 triethylamine (0.07 mL, 0.518 mmol). The reaction mixture was stirred for overnight and then quenched by water and extracted with ethyl acetate. Drying over magnesium sulfate, evaporation of the ethyl acetate and purification by column chromatography gave No.282 2-(4-(ethylsulfonamidomethyl)-3-fluorophenyl)-N-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide (example 83) in pure form (52 mg, 47percent).[0521]1H-NMR (400 MHz, CDCl3) delta 7.75 (d, 1H, J=6.40 Hz, Ar?H), 7.57 (d, 1H, J=6.36 Hz, Ar?H), 7.31 (m, 2H, Ar?H), 7.21 (m, 2H, Ar?H), 7.15 (d, 1H, J=5.92 Hz, Ar?H), 6.95 (m, 2H, Ar?H), 5.50 (m, 1H, amide-NH), 4.46 (m, 3H, amide-NH, Ar?CH2), 4.30 (d, 2H, J=5.04 Hz, Ar?CH2), 3.45 (q, 1H, J=5.68 Hz, amide-alpha-H), 2.97 (q, 2H, J=5.92 Hz, ethanesulfonly-2H), 2.37 (s, 1H, Ar?CH3), 1.43 (d, 3H, J=5.68 Hz, amide-3H), 1.30 (t, 3H, J=5.88 Hz ethanesulfonly-3H) |
79% | With pyridine; at 0℃; for 1h; | Step 1: No.72 (4-Bromo-2-fluorophenyl)methanamine (924 mg, 4.53 mmol) was dissolved in No.73 pyridine and No.171 ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at 0° C. The mixture was stirred for 1 h at 0° C. Then, the mixture was quenched with 1N No.56 HCl and extracted with ethyl acetate. Drying over magnesium sulfate and evaporation of the ethyl acetate and purified by column chromatography gave No.172 N-(4-bromo-2-fluorobenzyl)ethane-sulfonamide in pure form (1.06 g, 79percent). |
79% | With pyridine; at 0℃; for 1h; | Step 1 : (4-Bromo-2-fluorophenyl)methanamine (924 mg, 4.53 mmol) was dissolved in pyridine and ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at 0 °C. The mixture was stirred for 1 h at 0 °C. Then, the mixture was quenched with 1 N HCI and extracted with ethyl acetate. Drying over magnesium sulfate and evaporation of the ethyl acetate and purified by column chromatography gave N-(4-bromo-2-fluorobenzyl)- ethanesulfonamide in pure form (1 .06 g, 79 percent). |
79% | In pyridine; at 0℃; for 1h; | Step 1 : (4-Bromo-2-fluorophenyl)methanamine (924 mg, 4.53 mmol) was dissolved in pyridine and ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at 0 °C. The mixture was stirred for 1 h at 0 °C. Then, the mixture was quenched with 1 N HCI and extracted with ethyl acetate. Drying over magnesium sulfate and evaporation of the ethyl acetate and purified by column chromatography gave N-(4-bromo-2-fluorobenzyl)ethane- sulfonamide in pure form (1 .06 g, 79 percent). |
79% | With pyridine; at 0℃; for 1h; | Step 1: (4-Bromo-2-fluorophenyl)methanamine (924 mg, 4.53 mmol) was dissolved in pyridine and ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at 0° C. The mixture was stirred for 1 h at 0° C. Then, the mixture was quenched with 1N HCl and extracted with ethyl acetate. Drying over magnesium sulfate and evaporation of the ethyl acetate and purified by column chromatography gave N-(4-bromo-2-fluorobenzyl)-ethanesulfonamide in pure form (1.06 g, 79percent). |
79% | With pyridine; at 0℃; for 1h; | Step 1 : (4-Bromo-2-fluorophenyl)methanamine (924 mg, 4.53 mmol) was dissolved in pyridine and ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at 0 °C. The mixture was stirred for 1 h at 0 °C. Then, the mixture was quenched with 1 N HCI and extracted with ethyl acetate. Drying over magnesium sulfate and evaporation of the ethyl acetate and purified by column chromatography gave N-(4-bromo-2-fluorobenzyl)- ethanesulfonamide in pure form (1 .06 g, 79 percent). |
79% | With pyridine; at 0℃; for 1h; | Step 1 : 4-Bromo-2-fluorobenzylamine (924 mg, 4.53 mmol) was dissolved in pyridine and ethane sulfonyl chloride (0.82 mL, 8.60 mmol) was added to the solution at O °C. The mixture was stirred for 1 h at O °C. Then, the mixture was quenched with 1 N HCl and extracted with ethyl acetate (EtOAc). Drying (MgSO4) and evaporation of the ethyl acetate followed and the residue was purified by CC (eluent EtOAc/n-hexane) to yield N-(4-bromo-2- fluorobenzyl)ethanesulfonamide in pure form (1 .06 g, 79 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With triethylamine; In tetrahydrofuran; at 20℃; for 4h; | General procedure: Coumarin sulfonates 1-38 were synthesized by reactingdifferent hydroxylated coumarin derivatives (1 mmol) withcommercially available sulfonyl chlorides derivatives (1.2 mmol) inTHF (15 mL) and triethyl amine (1 mmol) was used as base. Reactionmixture was stirred for 4 h at room temperature to afford avariety of coumarin sulfonate esters 1e38. TLC monitoring wasused to determine the progress of the reaction. After the completionof reaction, THF was evaporated under reduced pressure andthe solid product obtained was washed with distilled water anddried under vacuum. The products were recrystallized in methanoland gave good yields. All the synthetic compounds 1-38 werecharacterized by different spectroscopic techniques such as EI-MS,HREI-MS, 1H-NMR, and 13C-NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.3% | With pyridine; In dichloromethane; at 20℃; for 12h; | A solution of <strong>[361345-40-6]tert-butyl 4-(3-aminobenzyl)piperazine-1-carboxylate</strong> (0.940 g, 3.226 mmol), pyridine (0.3 12 mL, 3.87 1 mmol) and ethanesulfonyl chloride (0.456 g, 3.548 mmol) in dichloromethane (30 mL) was stirred at the room temperature for 12 hr, Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated ammonium chloride solution, separated, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 12 g cartridge; ethyl acetate / hexane = 0 % to 40 %) to give tert-butyl 4-(3-(ethylsulfonamido)benzyl)piperazine- 1 -carboxylate as yellow solid (1.080 g, 87.3%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.3% | With pyridine; In dichloromethane; at 20℃; for 12h; | A solution of <strong>[7149-75-9]4-chloro-3-methylaniline</strong> (0.500 g, 3.53 1 mmol) and pyridine (0.427 mL, 5.297 mmol) in dichloromethane (20 mL) was mixed at the room temperature with ethanesulfonyl chloride (0.400 mL, 4.237 mmol) and stuffed at the same temperature for 12 hr. Then, aqueous 1M-hydrochloric acid solution was added to the reaction mixture, followed by extraction with dichloromethane. The bi-phasic mixture was passed through a plastic frit to remove the solid residues and aqueous layer, and the organic layer collected was concentrated in vacuo. The residue was chromatographed (Si02, 12 g cartridge; ethyl acetate / hexane = 5 percent to 50 percent) to give N(4-chloro-3-methylphenyl)ethanesulfonamide as beige solid (0.440 g, 53.3 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dipotassium hydrogenphosphate; In tetrahydrofuran; water; at 0 - 20℃; | A three-necked flask was charged with <strong>[62037-46-1]1-amino-3-chloropropyl-2-ol hydrochloride</strong> (14.60 g, 100 mmol) and tetrahydrofuran(73 mL), water (73 mL), stirred and cooled to 0 to 5 C, added with dipotassium hydrogen phosphate (34.84 g, 200 mmol), stirred for 5 minAfter the clockwise drop of ethyl sulfonyl chloride (13.50g, 105mm0l), plus the temperature after warming to room temperature for 3-4 hours, the end of the reaction0.5mol / L dilute hydrochloric acid 73mL quenching reaction, stirring and dispensing, water and then extracted with ethyl acetate 35mL 2 times, combined organic saturatedAnd washed with salt (73 mL), dried over anhydrous sodium sulfate and concentrated to give N-(3-chloro-2-hydroxypropyl) ethane sulfonamide Followed by the next step (GC purity of about 92%). |
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