Structure of 13457-28-8
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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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CAS No. : | 13457-28-8 |
Formula : | C6H4BrClN2O2 |
M.W : | 251.47 |
SMILES Code : | O=C(C1=NC(Cl)=CN=C1Br)OC |
MDL No. : | MFCD13195362 |
InChI Key : | NJAYXNFNZKQGNE-UHFFFAOYSA-N |
Pubchem ID : | 56923643 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.81 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.95 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.87 |
Solubility | 0.343 mg/ml ; 0.00136 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.67 |
Solubility | 0.54 mg/ml ; 0.00215 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.2 |
Solubility | 0.158 mg/ml ; 0.000628 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 |
-6.45 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.29 |
* 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 |
---|---|---|
87% | Into a 500 ml three-necked flask, 100 mL of acetic acid was added, and Compound 2 (20 g, 0.11 mol) was added dropwise to a 100 mL aqueous solution of 40% hydrogen bromide at 0C. The reaction was completed after 30 minutes of dropwise addition. A 50 ml aqueous solution of sodium nitrite (20.7 g, 0.33 mol) was added dropwise at a controlled temperature of 0C. After 30 minutes of reaction, the reaction is complete and it is quenched by the dropwise addition of 30 ml of 10% sodium bisulfite solution. Ethyl acetate extraction (200ml×2), dried over 20g of anhydrous sodium sulfate, The mixture was concentrated by suction filtration to obtain a white solid compound 3 (23.3 g, yield 87%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With lithium hydroxide monohydrate; In tetrahydrofuran; water; at 0℃; for 1h; | To a 250 ml three-neck flask was added 50 ml of tetrahydrofuran, 50 ml of water, and Compound 3 (20 g, 0.08 mol). Lithium hydroxide monohydrate (5 g, 0.12 mol) in water/70 ml of water was added dropwise. The reaction was completed at 0C for 1 hour. The reaction is complete. Methyl tert-butyl ether extraction (30 ml x 2). The aqueous phase was adjusted to pH=1 with 4N hydrochloric acid and extracted with dichloromethane (50 ml×3). Dry 10 g of anhydrous sodium sulfate and spin-dry to obtain white solid compound 4 (18 g, yield 96%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; | Take compound IV (1.3g, 5mmol), 2,3-dichlorophenylboronic acid (1.1g, 6mmol), K2CO3 (1.4g, 10mmol), Pd[P(C6H5)3]4 (0.3g, 0.25mmol) In a mixed solution of dioxane (18 mL)/water (2 mL), heat and stir at 100 C. under the protection of nitrogen until TLC indicates that the reaction is complete.After the reaction mixture was cooled to room temperature, it was poured into ice water (20 mL), stirred, and extracted with dichloromethane (20 mL×3). The extracted organic phases were combined, washed with water (50 mL×3), and dried over anhydrous sodium sulfate. The dried organic phase was evaporated on a rotary evaporator to remove the solvent, and the obtained residue was purified by column chromatography to obtain product X-1, 1.1 g, with a yield of 70%. |
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