Structure of 16932-45-9
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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. : | 16932-45-9 |
Formula : | C8H9BrO2 |
M.W : | 217.06 |
SMILES Code : | COC1=CC=CC(OC)=C1Br |
MDL No. : | MFCD07780177 |
Boiling Point : | No data available |
InChI Key : | VHVYSMMZHORFKU-UHFFFAOYSA-N |
Pubchem ID : | 612296 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.13 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.4 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.47 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.49 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.35 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.84 |
Solubility | 0.311 mg/ml ; 0.00143 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.22 |
Solubility | 1.3 mg/ml ; 0.006 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.51 |
Solubility | 0.0668 mg/ml ; 0.000308 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 |
-6.06 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) |
1.51 |
* 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 titanium tetrachloride; In dichloromethane; at -40 - 20℃; for 16h; | 2-Bromo-1,3-dimethoxybenzene (2.22 g, 10.2 mmol) dissolved into anhydrous dichloromethane (25 mL), chilled near -40 C. and treated over a few minutes with 1 M TiCl4 in dichloromethane (15.3 mL, 15.3 mmol) followed several minutes later with dichloro(methoxy)methane (1.0 mL, 11.1 mmol). The reaction mixture and Dewer flask were covered with insulation, allowed to warm slowly to ambient temperature for 16 hours and then poured over ice. The product was extracted into dichloromethane and the combined extracts were dried (Na2SO4), concentrated and chromatographed on silica (20 to 40% methyl tert-butyl ether/heptane) to give the title compound. 1H NMR (501 MHz, CDCl3) delta ppm 10.23 (d, J=0.8 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 6.82 (dd, J=8.8, 0.8 Hz, 1H), 3.99 (s, 3H), 3.99 (s, 3H)+ MS (DCI) m/z 245/247 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | EXAMPLES Production Example (A) Synthesis of Intermediate (A) [Show Image] (A-1) Synthesis of 1-bromo-2,6-dimethoxybenzene In the atmosphere of argon, 19.3g of 1,3-dimethoxybenzene and 500 mL of anhydrous diethyl ether were placed in a flask. 105 mL (1.6M) of a hexane solution of n-butyllithium was added, and the resulting reaction solution was stirred with heating for 4 hours. After cooling to room temperature while stirring, the reaction solution was cooled to -50C, followed by dropwise addition of 25g of bromine. Then, while heating the reaction solution to room temperature, stirring was conducted for 2 hours. Then, 300 mL of an aqueous 10% sodium thiosulfate solution was added, and the resulting mixture was stirred for 1 hour. The reaction solution was extracted with ether, and an aqueous phase was removed, and then, an organic phase was washed with saturated saline. The organic phase was dried with magnesium sulfate and concentrated. Residues were purified by means of silica gel column chromatography. The resulting crystals were washed with hexane, whereby 17.9g (yield: 52%) of white crystals of 1-bromo-2,6-dimethoxybenzene were obtained. | |
52% | Under an argon atmosphere 1,3-dimethoxy benzene (19.3g), was charged with anhydrous diethyl ether (500mL) to the flask, added 1.6M n-butyl lithium in hexane solution (105mL), the reaction solution was stirred for 4 hours under heating. After cooling to room temperature with continuous stirring, cooled to -50 C., was added dropwise bromine (25 g). The reaction solution was stirred for 2 hours while warming to room temperature. 10% aqueous solution of sodium thiosulfate (300mL) added, and the mixture was stirred for 1 hour. The reaction solution was extracted with ether, after removing the aqueous layer, the organic layer was washed with saturated brine. The organic layer was dried over magnesium sulfate, concentrated, and the residue was purified by silica gel chromatography. The obtained crystals were washed with hexane to obtain Intermediate 14 (17.9g). The yield was 52%. |
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