Structure of 17789-14-9
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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. : | 17789-14-9 |
Formula : | C9H9BrO2 |
M.W : | 229.07 |
SMILES Code : | BrC1=CC(C2OCCO2)=CC=C1 |
MDL No. : | MFCD00003209 |
InChI Key : | VYPYKCPWNPPBBX-UHFFFAOYSA-N |
Pubchem ID : | 87306 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.44 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.36 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.84 |
Solubility | 0.334 mg/ml ; 0.00146 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 2.11 mg/ml ; 0.00923 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.34 |
Solubility | 0.105 mg/ml ; 0.00046 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 |
-6.26 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) |
1.97 |
* 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 |
---|---|---|
347 mg | The preparation method is as follows:Ethylene glycol acetal (458 mg, 2 mmol) of 3-bromobenzaldehyde,Dissolved in 5 mL of dry tetrahydrofuran,N-Butyllithium (0.8 mL, 2 mmol) was slowly added dropwise at -70 C,One hour later, N-methyl-N-methoxy 4-fluorobenzamide was added slowly at -70 C(311 mg, 1.7 mmol),The reaction was continued at -70 C for 2 hours,The reaction was quenched by adding 5 mL saturated brine and the organic phase was extracted with ethyl acetate (10 mL * 3)The combined organic phases are dried over anhydrous sodium sulphate. Spin the solvent,Column chromatography (petroleum ether: ethyl acetate = 20: 1 as eluant),The reaction product 347mg.The reaction product was dissolved in 5 mL of dry methanol,1mL6N hydrochloric acid was added at room temperature, the reaction for 1 hour,The reaction was quenched by addition of saturated sodium bicarbonate solution,The organic phase was extracted with ethyl acetate (10 mL * 3), the organic phases were combined,Drying over anhydrous sodium sulfate. Spin the solvent,Column chromatography (petroleum ether: ethyl acetate = 20: 1 as eluant),The reaction product of 3- (4-fluorobenzoyl) acylbenzaldehyde 264mg, 68% yield in two steps. | |
1.37 g | To a solution of n-BuLi (9.31 mL, 14.89 mmol, 1.6 M) in dry THF(20 mL) at -78 C under nitrogen atmosphere, Compound 2 (1.71 g,7.45 mmol) in THF (12 mL) solution was added dropwise. Then, the solution was stirred at -78 C under nitrogen atmosphere for 1.5 h. Compound 1 (1.50 g, 8.19 mmol) in THF (12 mL) solution at -78 C was added. After the reaction was stirred to complete, the mixture was filtered, and the solvent was removed under reduced pressure. The residue was washed with water, extracted with DCM and purified bysilica gel column chromatography using petroleum ether/ethyl acetate (20:3) to give colourless oil Compound 3 (1.37 g, 5.05 mmol). The Compound 3 (1.37 g, 5.05 mmol) was dissolved in acetonitrile (10 mL),then the solution was added 2M HCl (8 mL, 15.14 mmol) and stirred at 25 C overnight. After the reaction was stirred to complete, the mixture was filtered, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleumether/ethyl acetate (10:1) to give colourless oil Compound 5b (869.52 mg, 3.81 mmol, 51.2% yield for 2 steps). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | To a solution of 4-fluorophenol (500mg, 4.46mol) in dry DCM (10ml), (3-formylphenyl)boronic acid(1.00g, 6.69mol), Cu(OAc)2 (811mg, 4.46mol) and Et3N (135.6mg, 1.34mol) were added under O2 atmosphere and the mixture was stirred at 25C for 48h. The mixture was diluted with brine and extracted with EtOAc. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether/ethyl acetate (10:1) to produce 0.22g of 0.22g with a yield of 22%. To a solution of 4-fluorophenol (500mg, 4.46mol) in dry DCM (10ml), (3-formylphenyl)boronic acid(1.00g, 6.69mol), Cu(OAc)2 (811mg, 4.46mol) and Et3N (135.6mg, 1.34mol) were added under O2 atmosphere and the mixture was stirred at 25C for 48h. The mixture was diluted with brine and extracted with EtOAc. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether/ethyl acetate (10:1) to produce 0.22g of 0.22g with a yield of 22%. |
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