Structure of 6344-72-5
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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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Search for reports by entering the product batch number.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 6344-72-5 |
Formula : | C9H8N2 |
M.W : | 144.17 |
SMILES Code : | CC1=CC=C2N=CC=NC2=C1 |
MDL No. : | MFCD00041001 |
InChI Key : | OSRARURJYPOUOV-UHFFFAOYSA-N |
Pubchem ID : | 242567 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 44.5 |
TPSA ? Topological Polar Surface Area: Calculated from |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.74 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.36 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.94 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.45 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.73 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.26 |
Solubility | 0.786 mg/ml ; 0.00545 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.5 |
Solubility | 4.52 mg/ml ; 0.0313 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.69 |
Solubility | 0.0294 mg/ml ; 0.000204 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 |
-6.21 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 |
1.0 |
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) |
1.26 |
* 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 |
---|---|---|
35% | With N-Bromosuccinimide;dibenzoyl peroxide; In tetrachloromethane; for 48h;Reflux; | A mixture of 6-methylquinoxaline (2.0 g, 13.9 mmol), N-bromosuccinimide (3.0 g, 16.9 mmol), and benzoyl peroxide (411 mg, 1.7 mmol) in anhydrous carbon tetrachloride (50 mL) was stirred at reflux for 2 days. Dichloromethane (50 mL) was added after cooling to room temperature. The mixture was extracted with 1 N NaOH (1 x 100 mL) and brine (1 x 100 mL). The organic extract was recovered, dried over MgSO4, filtered, evaporated, and dried in vacuo. The crude product was purified by flash chromatography (0-30% EtOAc/hexanes), affording 6- (bromomethyl)quinoxaline (1.10 g, 35% yield). |
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 18h;Inert atmosphere; Reflux; | Intermediate 17: 6-(bromomethyl)quinoxaline A mixture of 6-methylquinoxaline (300 mg), NBS (370 mg) and benzoyl peroxide (5.04 mg) in carbon tetrachloride (8 ml.) was heated at reflux under an atmosphere of argon for 18 hr. The reaction mixture was cooled to RT, filtered and concentrated under reduced pressure to give a brown oil. The crude product was purified by column chromatography (Biotage SP4, 40+M column, 20-100% EtOAc / isohexane. The fractions containing product were combined and concentrated under reduced pressure to give the title compound (243 mg) as a white solid, m/z [M+H]+: 223.1 / 225.0. Retention time 0.80 min (LC/MS method 3). | |
With N-Bromosuccinimide; dibenzoyl peroxide; | Example 292 Synthesis of 6-(bromomethyl)quinoxaline. To a solution of 6-methylquinoxaline (5 g, 34.7 mmol) in DCE (100 mL) was added NBS (7.12 g, 40 mmol) and benzoyl peroxide (840 mg, 3.47 mmol). The reaction mixture was stirred at 85 C. for 16 h under nitrogen. H2O (100 mL) was added, and the mixture was extracted with DCM (150 mL*3). The combine organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product which was purified by silica gel chromatography (PE/EtOAc=1/1) to give 6-(bromomethyl)quinoxaline as a yellow solid. (5.5 g, 71%). ESI-MS [M+H]+: 224.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23%; 77% | With N-Bromosuccinimide; dibenzoyl peroxide; In benzene; for 5h;Heating / reflux; | Example 9 6-Bromomethylquinoxaline: A mixture of 6-methylquinoxaline (1.5 g, 10.4 mmol), N-bromosuccinimide (2.2 g, 12.5 mmol) and benzoylperoxide (0.30 g, 1.25 mmol) in benzene (35 mL) was stirred rapidly and heated to reflux for 5 h. Upon cooling the mixture was diluted with ethyl acetate (25 mL), washed with 1N sodium hydroxide solution (50 mL) and saturated sodium chloride solution (50 mL). The organic layer was dried (MgSO4) and evaporated to a crystalline solid (2.5 g, 77% desired product, 23% alpha,alpha-dibrominated product as determined by 1H NMR). The mixture was used in subsequent reactions. |
23%; 77% | With N-Bromosuccinimide; dibenzoyl peroxide; In benzene; for 5h;Heating / reflux; | 6-Bromomethyl-quinoxaline: A mixture of 6-methylquinoxaline (1.5 g, 10.4 mmol), N-bromosuccinimide (2.2 g, 12.5 mmol) and benzoylperoxide (0.30 g, 1.25 mmol) in benzene (35 mL) was stirred rapidly and heated to reflux for 5 h. Upon cooling, the mixture was diluted with ethyl acetate (25 mL), washed with IN sodium hydroxide solution (50 mL) and saturated sodium chloride solution (50 mL). The organic layer was dried (MgSO4) and evaporated to a crystalline solid (2.5 g, 77% desired product, 23% alpha,alpha-dibrominated product as determined by 1H NMR). The mixture was used in subsequent reactions. |
36% | With N-Bromosuccinimide;2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 2h;Heating / reflux; | 6-Bromomethylquinoxaline (1) (De Selms, R. C.; Greaves, R. J., Scheigh, W. R. J. Het. Chem. 1974, 11, 595); Bromomethylquinoxaline is unstable and decomposes when stored for long time. It should be used up within a day or two of its preparation. To a clear solution of 6-methylquinoxaline (60 g, 0.416 mol) in 550 mL of CCl4 was added in one portion solid NBS (Aldrich, 81.5 g, 0.458 mol, 1.1 eq) and AlBN (Aldrich, 1.6 g, 9.7 mmol, 2.3 mol %). The resulting mixture was heated at reflux for 2 hr and cooled to rt. The precipitate of succinimide was removed by filtration. The filtrate was evaporated on rotary evaporator until solid begins to crystallize out of the solution. Remaining mixture was left at rt for 2 hr, then the crystallized product was filtered off, washed with small amount of hexanes-CCl4 mixture (ca. 20:1) and dried in vacuum. The isolated solid contained just traces of the di-bromo side-product and was used in the following step without further purification. Yield 33.3 g (36%) as colorless crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; dibenzoyl peroxide; In 1,2-dichloro-ethane; | Example 3 Preparation of a Solid Sample of 6-bromomethyl-quinoxaline In a 100 ml flask, 6-methyl-quinoxaline (2.5 g, 17.4 mmol) was dissolved together with N-bromosuccinimide (4.63 g, 19 mmol) and benzoyl peroxide (0.3 g, 1.24 mmol) in 70 g of 1,2-dichloroethane. The solution was refluxed for 150 minutes and analyzed. The concentrations of the reactants and some of their molar ratios are shown below: The solution was cooled in the freezer overnight and the solid residue was separated by filtration. The solid was washed with pentane and the washings were combined with the liquid fraction. The clear reddish solution was then vacuum dried to give an orange solid that was used in the preparation of 6-hydroxymethyl-quinoxaline. |