Structure of 169044-96-6
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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. : | 169044-96-6 |
Formula : | C9H10BrNO3 |
M.W : | 260.08 |
SMILES Code : | O=C(OC)C1=CC(Br)=C(OC)C=C1N |
MDL No. : | MFCD21868787 |
Boiling Point : | No data available |
InChI Key : | SFXCMXLNSVHKCE-UHFFFAOYSA-N |
Pubchem ID : | 19701951 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P264-P270-P301+P312-P330 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 56.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
61.55 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.31 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.77 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.03 |
Solubility | 0.244 mg/ml ; 0.00094 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.24 |
Solubility | 0.149 mg/ml ; 0.000574 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.1 |
Solubility | 0.208 mg/ml ; 0.000798 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) |
No |
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 |
-6.25 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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.76 |
* 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 |
---|---|---|
82.06% | With bromine; In dichloromethane; at 20℃; for 20h; | To a solution of compound 34 (4.0 g, 0.02 mol) in DCM(200 mL) was added bromine (1.36 mL, 0.02 mol). Themixture was stirred at room temperature for 20 h. It wasdiluted with saturated sodium hydrogen sulfite (50 mL) andthe aqueous solution was extracted with DCM. The combinedorganic layers were washed with brine, dried overNa2SO4 and filtered. The residue was purified by silica gelcolumn chromatography eluting with PE/EA to give whitepowder 35 (4.71 g, 82.06%). 35: 1H NMR delta (400 MHz,CDCl3) 8.04 (s, 1H), 6.14 (s, 1H), 5.87 (s, 2H), 3.89 (s, 3H),3.87 (s, 3H). |
With bromine; In chloroform; at 0 - 20℃; | A-8a (15.0 g, 82.8 mmol, LO equiv.) is dissolved in chloroform (750 mL) and cooled to 0 C. A solution of bromine (4.2 mL, 82.8 mmol, 1.0 equiv.) in chloroform (10 mL) is added dropwise and the reaction mixture stirred for 1 h at rt. Then the reaction mixture is quenched with sodium thiosulphate (aqu.) and extracted with EtOAc. The combined organic layer is washed with saturated NaHC03 solution, dried over Na2S04 and concentrated in vacuo. The crude product is washed with hexane to give the final compound A-9b (HPLC method: GVK_LCMS_05: tret [min] = 1 .76; [M+H]+ = 260.0). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.5 g | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.0h; | Step 2: Methyl 2-amino-5-bromo-4-methoxybenzoateTo a stirred suspension of <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (6.3 g, 0.025 mol) and potassium carbonate (7.06 g, 0.051 mol) in N,ll-dimethyl formamide (63 mL) was added methyl iodide (5.45 g, 0.038 mol) dropwise at 0C. After the addition was complete, the reaction mixture was stirred at room temperature for 1 h. The mixture was poured into ice cold water (500 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with water (100 mL) followed by brine solution, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure and the crude product was purified using column chromatography (100-200 mesh silica gel, 20% EtOAc in hexane) to afford the title compound as white solid (5.5 g, 83% yield). *H NMR (400 MHz, DMSO-d6) : delta 7.78 (s, 1H), 6.85 (brs, 2H), 6.44 (s, 1H), 3.80 (s, 3H), 3.75 (s, 3H). ESI-MS: Calculated mass: 258.98; Observed mass: 258.3 [M-H] |
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