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Structure of 23095-05-8
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 23095-05-8 |
Formula : | C7H6BrClO3S |
M.W : | 285.54 |
SMILES Code : | O=S(C1=CC(Br)=CC=C1OC)(Cl)=O |
MDL No. : | MFCD00051768 |
InChI Key : | IXSBNNRUQYYMRM-UHFFFAOYSA-N |
Pubchem ID : | 520020 |
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 | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 53.72 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.47 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.97 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.02 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.46 |
Solubility | 0.0981 mg/ml ; 0.000343 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.35 |
Solubility | 0.129 mg/ml ; 0.00045 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.91 |
Solubility | 0.0348 mg/ml ; 0.000122 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) |
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 |
-6.19 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.19 |
* 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 |
---|---|---|
61% | EXAMPLE 36 5-Bromo-2-methoxy-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide 5-Bromo-2-methoxy-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide was prepared from <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> and 5-bromo-2-methoxybenzenesulfonyl chloride according to the procedures described in Example 5. The crude product was purified by recrystallization from ethyl acetate/hexanes to give a crystalline solid, m.p. 92-195 C., yield 61%. | |
61% | EXAMPLE 76 5-Bromo-2-methoxy-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide 5-Bromo-2-methoxy-N-(4-bromo-3-methyl-5-isoxazolyl)benzenesulfonamide was prepared from <strong>[33084-49-0]5-amino-4-bromo-3-methylisoxazole</strong> and 5-bromo-2-methoxybenzenesulfonyl chloride according to the procedures described in Example 45. The crude product was purified by recrystallization from ethyl acetate/hexanes to give a crystalline solid, m.p. 192-195 C., yield 61%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With pyridine; In tetrahydrofuran; | Example 20.2.1 Methyl 3-[(5-bromo-2-methoxyphenyl)sulfonyl]amino}-3-phenylpropanoate At 0 C., a solution of 10.73 g (37.59 inmol, 1.0 equiv.) (5-bromo-2-methoxyphenyl)sulfonyl chloride in 20 ml dry tetrahydrofurane is added to a solution of 8.51 g (39.47 mmol, 1.05 equiv.) <strong>[22838-46-6]methyl 3-amino-3-phenylpropionate hydrochloride</strong> and 30.4 ml (375.9 mmol, 10 equiv.) pyridine in 40 ml dry tetrahydrofiarane. After the addition is completed, the cooling bath is removed and stirring continued over night. A white precipitate is formed. Most of the solvent and the pyridine is removed on a rotatory evaporator. The residue is acidified with dilute hydrochloric acid and the product is extracted with dichloromethane. The organic layer is successively washed with water and brine. Dried over unhydrous sodium sulfate. The crude product is purified by crystallization from ethyl acetate to afford 13.33 g (31.12 mmol, 78% yield) as a white solid. Mass spectrometry (DCI/NH3): 445/447 (M+NH4+) Retention time (TLC): Rf=0.48 (dichloromethane/methanol, 100:2) 1H-NMR (400 MHz, dimethylsulfoxide-d6): delta=8.15 (1H, d), 7.57 (1H, d), 7.53 (1H, dd), 7.09 (5H, m), 6.81 (1H, d), 4.62 (1H, quart), 3.71 (3H, s), 3.48 (3H, s), 2.87 (1H, dd), 2.68 (1H, dd). |
78% | With pyridine; In tetrahydrofuran; at 0℃; | At 0C, a solution of 10.73 g (37.59 mmol, 1.0 equiv.) (5-bromo-2-methoxyphenyl)sulfonyl chloride in 20 ml dry tetrahydrofurane is added to a solution of 8.51 g (39.47 mmol, 1.05 equiv.) <strong>[22838-46-6]methyl 3-amino-3-phenylpropionate hydrochloride</strong> and 30.4 ml (375.9 mmol, 10 equiv.) pyridine in 40 ml dry tetrahydrofurane. After the addition is completed, the cooling bath is removed and stirring continued over night. A white precipitate is formed. Most of the solvent and the pyridine is removed on a rotatory evaporator. The residue is acidified with dilute hydrochloric acid and the product is extracted with dichloromethane. The organic layer is successively washed with water and brine. Dried over unhydrous sodium sulfate. The crude product is purified by crystallization from ethyl acetate to afford 13.33 g (31.12 mmol, 78% yield) as a white solid. Mass spectrometry (DCI/NH3): 445/447 (M+NH4+) Retention time (TLC): Rf = 0.48 (dichloromethane/methanol, 100:2) 1H-NMR (400 MHz, dimethylsulfoxide-d6): delta = 8.15 (1H, d), 7.57 (1H, d), 7.53 (1H, dd), 7.09 (5H, m), 6.81 (1H, d), 4.62 (1H, quart), 3.71 (3H, s), 3.48 (3H, s), 2.87 (1H, dd), 2.68 (1H, dd). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; In pyridine; at 60℃; | To a solution of 6-morpholinopyridin-3 -amine (80 mg, 0.45 mmol) in pyridine (5 mL) was added 5-bromo-2-methoxybenzene-l-sulfonyl chloride (126 mg, 0.45 mmol) and DMAP (10 mg), and the mixture was stirred at 60 C overnight. LCMS showed that the reaction was complete. The resultant was concentrated in vacuum to remove pyridine and the residue was diluted with DCM (20 mL). The mixture was washed with IN HCl (15 mL), dried over Na2S04 amd concentrated in vacuum. The crude product was purified by prep-TLC (DCM/MeOH, 15/1) to give 30 mg (yield: 16%) of 5-bromo-2-methoxy-N-(6-morpholinopyridin-3- yl)benzenesulfonamide as a white solid. [00645] 1H NMR (DMSO-d6, 400 MHz): delta = 9.72 (1H, brs), 7.80-7.76 (2H, m), 7.64 (1H, d), 7.23 (1H, d), 7.20 (1H, d), 6.72 (1H, d), 3.94 (3H, s), 3.64 (4H, t), 3.35-3.30 (4H, m). MS: m/z 428.0 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In dichloromethane; at 20℃; | General procedure: To 5-bromo-2-methoxy-benzenesulfonyl chloride (500 mg, 1.76 mmol) and <strong>[191478-99-6]methyl 4-amino-2,6-difluorobenzoate</strong> (395 mg, 2.11 mmol), dichloromethane (12 ml) and pyridine (427 mul, 5.28 mmol) were added, followed by stirring at room temperature overnight. The reaction solution was concentrated under reduced pressure, diluted with dichloromethane, washed with 2 N hydrochloric acid, water, and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained product was dissolved in ethanol (5.0 ml) and DMF (5.0 ml), and 10% Pd/C (50 mg) was added thereto, followed by stirring overnight in a hydrogen atmosphere at 3 atm. After filtration through Celite, the filtrate was concentrated under reduced pressure, and tetrahydrofuran (5.0 ml) and water (1.0 ml) were added thereto. Then, a 2 N aqueous sodium hydroxide solution (2.0 ml) was added dropwise thereto, followed by stirring at room temperature for 4 hours. The mixture was neutralized with 2 N hydrochloric acid, and concentrated under reduced pressure. Then, the obtained residue was purified by reversed-phase HPLC (H2O containing 0.10 TFA/CH3CN system), followed by freeze-drying, to obtain the title compound |