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Structure of 15084-51-2
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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. : | 15084-51-2 |
Formula : | C10H13ClO2S |
M.W : | 232.73 |
SMILES Code : | O=S(C1=CC=C(C(C)(C)C)C=C1)(Cl)=O |
MDL No. : | MFCD00007449 |
InChI Key : | YEZADZMMVHWFIY-UHFFFAOYSA-N |
Pubchem ID : | 139882 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 58.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.52 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.43 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.62 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.99 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.76 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.05 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.75 |
Solubility | 0.0415 mg/ml ; 0.000178 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.2 |
Solubility | 0.0147 mg/ml ; 0.000063 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.16 |
Solubility | 0.0162 mg/ml ; 0.0000698 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-5.15 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.68 |
* 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 |
---|---|---|
21% | In tetrahydrofuran; methanol; water; mineral oil; | EXAMPLE 39 4-tert-Butyl-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (354 mg, 2.0 mmol) in dry THF (1 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 188 mg, 4.4 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 10 min., the reaction was warmed to room temperature for 10 min. to complete the reaction. The reaction mixture was re-cooled to 0 C. and 4-tert-butylbenzenesulfonyl chloride (512 mg, 2.2 mmol) was added slowly. Stirring was continued for 20 min. at 0-5 C. Excess sodium hydride was decomposed by addition of methanol (0.4 ml) followed by water (0.5 ml). The mixture was acidified with hydrochloric acid and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give a crude product, which was purified by recrystallization from ethyl acetate/hexanes to give a white solid in 21% yield, m.p. 170 C. (dec.). |
21% | In tetrahydrofuran; methanol; water; mineral oil; | EXAMPLE 5 4-tert-Butyl-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (354 mg, 2.0 mmol) in dry THF (1 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 188 mg, 4.4 mmol)in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 10 min., the reaction was warmed to room temperature for 10 min. to complete the reaction. The reaction mixture was re-cooled to 0 C. and 4-tert-butylbenzenesulfonyl chloride (512 mg, 2.2 mmol) was added slowly. Stirring was continued for 20 min. at 0-5 C. Excess sodium hydride was decomposed by addition of methanol (0.4 ml) followed by water (0.5 ml). The mixture was acidified with hydrochloric acid and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give a crude product, which was purified by recrystallization from ethyl acetate/hexanes to give a white solid in 21% yield, m.p. 170 C. (dec.). |
21% | In tetrahydrofuran; methanol; water; mineral oil; | EXAMPLE 39 4-tert-Butyl-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (354 mg, 2.0 mmol) in dry THF (1 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 188 mg, 4.4 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 10 min., the reaction was warmed to room temperature for 10 min. to complete the reaction. The reaction mixture was re-cooled to 0 C. and 4-tert-butylbenzenesulfonyl chloride (512 mg, 2.2 mmol) was added slowly. Stirring was continued for 20 min. at 0-5 C. Excess sodium hydride was decomposed by addition of methanol (0.4 ml) followed by water (0.5 ml). The mixture was acidified with hydrochloric acid and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give a crude product, which was purified by recrystallization from ethyl acetate/hexanes to give a white solid in 21% yield, m.p. 170 C. (dec.). |
21% | In tetrahydrofuran; methanol; water; mineral oil; | EXAMPLE 45 4-tert-Butyl-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide A solution of <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> (354 mg, 2.0 mmol) in dry THF (1 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 188 mg, 4.4 mmol) in dry THF (1 ml) at 0-5 C. After stirring at 0-5 C. for 10 min., the reaction was warmed to room temperature for 10 min. to complete the reaction. The reaction mixture was re-cooled to 0 C. and 4-tert-butylbenzenesulfonyl chloride (512 mg, 2.2 mmol) was added slowly. Stirring was continued for 20 min. at 0-5 C. Excess sodium hydride was decomposed by addition of methanol (0.4 ml) followed by water (0.5 ml). The mixture was acidified with hydrochloric acid and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure to give a crude product, which was purified by recrystallization from ethyl acetate/hexanes to give a white solid in 21% yield, m.p. 170 C. (dec.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With triethylamine; In dichloromethane; at 0 - 20℃; for 6h; | General procedure: 2-(Piperazin-1-yl)benzazolyl derivatives 8a-d (1 equivalent) and triethylamine (1.5 equivalents) were dissolved in 25 ml dry CH2Cl2 and cooled to 0C in an ice salt bath. Then the required phenylsulfonyl chloride (1.1 equivalents) dissolved in 20 ml dry CH2Cl2 was added dropwise. After the addition, the reaction mixture was stirred at 0C for a further 1h and then allowed to warm to room temperature and the course of the reaction followed by TLC. After completion, the mixture was diluted with additional 50 ml of CH2Cl2 and extracted with 10% NaHCO3 solution (3 x 50 ml). The organic phase was washed with dist. H2O, sat. NaCl solution, dried over anhyd. Na2SO4, filtered and evaporated to dryness. The product was recrystallised from the appropriate solvent, the precipitate formed was filtered under suction and dried at 60C under high vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With pyridine; In chloroform; at 0 - 100℃; for 12.0h; | To a stirred solution of compound LXVIII (3 g, 21.12 mmol) in chloroform (60 ml) was addedpyridine (15 ml) at 0C followed by addition of 4-tert-butylbenzenesulfonyl chloride (XI, 5.89g, 25.34 mmol). The reaction mixture was heated at 100C for 12 h, cooled to room temperature and concentrated under reduced pressure. The crude material was diluted with a saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine solution, dried over anhydrous Na2SO4 and evaporated under reducedpressure to afford 4-(tert-butyl)-N-(5 -chloro-6-methylpyridin-2-yl)benzenesulfonamide(LXIX; 6 g, 84% yield). ?H NMR (400 MHz, DMSO-d6) oe 11.11 (bs, 1H), 7.86-7.84 (d, J8.4 Hz, 2H), 7.72-7.70 (d, J 8.8 Hz, 1H), 7.60-7.58 (d, J 8.4 Hz, 2H), 6.94-6.93 (d, J= 7.6Hz, 1H), 2.36 (s, 3H), 1.27 (s, 9H). MS (M+1): 339.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine; In methanol; at 20℃; | General procedure: Solutions of selected methyl ketones (2 mmol) in methanol(6 mL) were stirred and corresponding sulfonylchlorides (2.4 mmol) were added. Then, triethylamine(0.6 mL) was added dropwise. The mixtures were stirredovernight at room temperature. After completion of thereactions, mixtures were poured into iced water withstirring. In some cases (for our compounds 7f, 7g, 8e, 8f,8g, and 9g; see below), the formed precipitate was filteredand washed with cold diethyl ether. In other cases, whenno precipitate formed, the organic layer was extractedwith dichloromethane (3 × 50 mL), dried over anhydrousNa2SO4 and evaporated under vacuum. The residue waspurified by short column chromatography on silica gel,using dichloromethane as eluent. The oil obtained usuallycrystallized; if not, the oily residue was dissolved indiethyl ether from which products crystallized on standingin a deepfreeze. Crude products were washed with coldether, and 21 pure, mostly white crystals were obtained, asfollows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.9% | 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 |
---|---|---|
75% | at 20℃; for 24h;Cooling with ice; Inert atmosphere; | General procedure: The acid or sulfonyl chloride (1.0-1.1 equiv.) was added in one go to an ice-cooled solution of the appropriate amine or amine hydrochloride (1.0-1.1 equiv.) and diisopropylethylamine, triethylamine or pyridine (2.0-3.0 equiv.) in CH2Cl2 or chloroform (0.1-0.2M) and stirred at RT. After 24h, the reaction was quenched with 1M HCl. The layers were separated, and the aqueous layer was extracted with CH2Cl2. The organic layer was dried (MgSO4), filtered and concentrated in vacuo, and column chromatography isolated the target compound. |
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