Structure of 66490-33-3
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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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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 66490-33-3 |
Formula : | C8H5ClS |
M.W : | 168.64 |
SMILES Code : | ClC1=C(C=CS2)C2=CC=C1 |
MDL No. : | MFCD18451627 |
InChI Key : | YGYUMNQONHLLNC-UHFFFAOYSA-N |
Pubchem ID : | 12398605 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.84 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.8 |
Solubility | 0.0267 mg/ml ; 0.000158 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.85 |
Solubility | 0.0239 mg/ml ; 0.000142 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.95 |
Solubility | 0.0189 mg/ml ; 0.000112 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 |
-4.79 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<2.0 |
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 |
---|---|---|
With phosphoric acid; In chlorobenzene; for 6h;Heating / reflux; | A solution containing polyphosphoric acid (8 g) and chlorobenzene (50 mL) is heated at reflux. A solution containing 1-chloro-3-(2,2-dimethoxyethylsulfanyl)benzene (2.7 g, 11.6 mmol) in chlorobenzene (5 mL) is added dropwise to the refluxing polyphosphoric acid solution. After 6 hours, the solution is cooled to ambient temperature. The solution is diluted with CH2Cl2 and washed with water and saturated NaCl (aq.). The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with hexanes to yield the title compounds (2.4 g, 9.0 mmol) as a 1:1 isomeric mixture. 1H NMR (CDCl3, 300 MHz) δ7.88 (m, 1H), 7.75 (m, 2H), 7.42 (m, 2H). MS (EI): m/z 168, 170 (M+), Cl pattern |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of 4-chloro-benzo[b]thiophene and <strong>[66490-20-8]6-chlorobenzo[b]thiophene</strong> (11.8 g, 88.1 mmol), in 400 mL of THF at -78 C. is added n-BuLi (55 mL of a 1.6M solution in hexanes, 88.1 mmol). After 15 minutes, the solution is added by cannula to a precooled (-78 C.) solution of SO2 (200 g) in 100 mL of THF. After addition, the solution is allowed to warm to ambient temperature. After 0.5 hour, the solution is concentrated. The residue is suspended in hexanes (400 mL) and is cooled to 0 C. To the solution is added SO2Cl2 (12.5 g, 92.5 mmol). After stirring for 15 minutes, the solution is concentrated. The residue is dissolved in EtOAc. The organic solution is washed with saturated NH4Cl (aq.), H2O and saturated NaCl (aq.). The organic layer is dried over MgSO4, filtered and concentrated. The crude product is dissolved in CH2Cl2 and filtered through a plug of silica gel. The crude product is purified by column chromatography eluting with hexanes to yield the title compound as well as 4-chlorobenzo[b]thiophene-2-sulfonyl chloride as white solids. [1511] 4-Chlorobenzo[b]thiophene-2-sulfonyl chloride: 1H NMR (CDCl3, 300 MHz) δ8.32 (m, 1H), 7.81 (m, 1H), 7.53 (m, 2H). [1512] 6-Chlorobenzo[b]thiophene-2-sulfonyl chloride: 1H NMR (CDCl3, 300 MHz) δ8.11 (s, 1H), 7.88 (m, 2H), 7.50 (m, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51%; 40% | With PPA; Polyphosphoric acid (PPA); In chlorobenzene; for 3.75h;Heating / reflux; | Preparation of 4-Chlorobenzo[b]thiophene and 6-Chlorobenzo[b]thiophene. [CHEMMOL-00085] [0265] A mixture of 3-chlorobenzenethiol (9.9 g, 68.5 mmol), K2CO3 (11.35 g, 82.1 mmol), and bromoacetaldehyde diethyl acetal (8.1 mL, 68.5 mmol) in acetone (250 mL) was stirred at room temperature for 24 h. The base and the salt formed were removed by filtration with ethereal rinse. The filtrate and washings were combined, concentrated, taken up in 250 mL of Et2O, and washed with 200 mL each of 0.5 N KOH and brine. The aqueous layers were back-extracted with 2×250 mL of Et2O. Combined organic layers were dried over MgSO4, concentrated, and dried under vacuum. [0266] To a heated and vigorously stirred biphasic solution of polyphosphoric acid (PPA) (ca. 35 g) and chlorobenzene (350 mL) was added dropwise the crude acetal in 100 mL of chlorobenzene over 2.5 h period. After heating at reflux for 1.25 h, the mixture was stirred overnight while allowed to cool to room temperature. The organic layer was separated by decantation, concentrated, taken up in EtOAc (300 mL), and washed with 200 mL each of saturated aqueous NaHCO3 and brine. The PPA layer was dissolved in H2O (ca. 500 mL) and extracted with 3×300 mL of EtOAc which was washed with the saturated aqueous NaHCO3 and brine used above. Combined organic layers were dried over MgSO4, concentrated, and purified by PrepLC 500A with hexanes as eluent to yield 4-chlorobenzo[b]thiophene (4.269 g, 40%) and 6-chlorobenzo[b]thiophene (5.896 g, 51%) which was contaminated with 3-chlorobenzenedisulfide. FDMS 168(M)+ |
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