Structure of 874792-20-8
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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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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'.
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CAS No. : | 874792-20-8 |
Formula : | C10H8BrNO |
M.W : | 238.08 |
SMILES Code : | COC1=CC=NC2=CC=C(Br)C=C12 |
MDL No. : | MFCD04036192 |
InChI Key : | AWLGLUBASOBKNM-UHFFFAOYSA-N |
Pubchem ID : | 45790929 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 55.94 |
TPSA ? Topological Polar Surface Area: Calculated from |
22.12 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 |
2.85 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.72 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.61 |
Solubility | 0.0578 mg/ml ; 0.000243 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.97 |
Solubility | 0.253 mg/ml ; 0.00106 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.69 |
Solubility | 0.00489 mg/ml ; 0.0000206 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) |
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 |
-5.73 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) |
1.49 |
* 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 |
---|---|---|
90.8% | In methanol; at 20 - 120℃; for 15h; | To a solution of 6-bromo-4-chloro-quinoline (12.12 g, 50 mmol) in methanol (200 mL) was added sodium methoxide (13.50 g, 250 mmol) at room temperature. Then, the reaction mixture was heated to 120 C. for 15 h in a sealed reaction flask. After cooling to room temperature, the methanol was removed under the vacuum and the residue was diluted with water. Then, the solids were collected by filtration and washed with water. After drying in air, 10.8 g (90.8% yield) of 6-bromo-4-methoxy-quinoline was isolated as a white solid which can be crystallized from acetonitrile: EI-HRMS m/e calcd for C10H8BrNO (M+) 236.9789, found 236.9784. |
36% | In methanol; at 120℃; for 1h;Microwave irradiation; | 300 mg (1.24 mmol) of 6-bromo-4-chloroquinoline [Lin et al., J. Med. Chem. 1978, 21, 268] was taken up in 4 ml methanol and 1.15 ml (6.19 mmol) methanolic sodium methylate solution (30 wt.%) was added. Then it was reacted in a single mode microwave for 1 h at 1200C. The solvent was removed in a rotary evaporator and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over magnesium sulfate. The solvent was removed by distillation at reduced pressure. In this way we obtained 150 mg (36% of theor.) of the target compound.LC-MS (method 2): R, = 1.24 min; MS (EIpos): m/z = 238 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 110℃;Inert atmosphere; | Under an argon atmosphere, 150 mg of example 87A was dissolved in 4 ml dioxane. Then 111.3 mg (1.134 mmol) potassium acetate, 41.2 mg (0.050 mmol) of 1, l'-bis-(diphenylphosphino)- ferrocene palladium(II) chloride-dichloromethane complex and 176 mg (0.693 mmol) of 4,4,4'4'5,5,5'5'-octamethyl-2,2'-bi-l,3,2-dioxaborolan were added. The reaction mixture was stirred overnight at 1100C oil bath temperature. After cooling, dichloromethane was added to the reaction mixture and it was filtered on kieselguhr. It was washed again with ethyl acetate. The filtrate was concentrated in a rotary evaporator at reduced pressure and dried under high vacuum. We obtained 227 mg of 4-methoxy-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)quinoline [47%, (LC-MS)] as raw product. This was reacted subsequently without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | To a solution of <strong>[874792-20-8]6-bromo-4-methoxy-quinoline</strong> (8.91 g, 37.42 mmol) in THF (tetrahydrofuran) (155 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (16.46 mL, 4.16 mmol, 1.1 equiv.) at -70 C. During the addition, the temperature of the reaction mixture was raised slightly to -60 C. and it gave a very dark brown solution. The resulting colored solution was stirred for 30 min at this temperature. Then, a solution of dimethylformamide (5.78 mL, 74.84 mmol) in THF (10 mL) was added dropwise. After addition, the mixture was allowed to warm to room temperature and stirred for 15 h. Then, the mixture was diluted with saturated ammonium chloride solution and the two layers were separated. The aqueous layer was extracted with ethyl acetate (3*1 50 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude brown solid. This solid was dissolved in acetonitrile (~50 mL) at hot condition and then stored in the refrigerator overnight. The solids were collected by filtration and washed with diethyl ether. After drying in air, 4.47 g (64% yield) of 4-methoxy-quinoline-6-carbaldehyde was isolated as a white solid: EI-HRMS m/e calcd for C11H9NO2 (M+) 187.0633, found 187.0638. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 100℃; for 1h; | A 5 mL microwave vial was charged with 4-chloro-6-bromoquinoline (0.15 g, 0.62 mmol) and a 25 wt % solution of sodium methoxide in methanol (2.0 mL, 8.8 mmol). The vial was sealed and heated to 100C for 60 minutes under microwave irradiation (Biotage, Initiator). After cooling, the solvent was removed in vacuo, the residue washed with water, filtered and dried via .yophilization to obtain 6-bromo-4-methoxyquinoline.LRMS (ESI) calc'd for C10H9BrNO [M+H]+: 238, Found: 238. |