Structure of 175422-04-5
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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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CAS No. : | 175422-04-5 |
Formula : | C5H2Br2N2O2 |
M.W : | 281.89 |
SMILES Code : | BrC1=NC(=CC(=C1)[N+](=O)[O-])Br |
MDL No. : | MFCD07369947 |
InChI Key : | XIPATZUHJFQGQC-UHFFFAOYSA-N |
Pubchem ID : | 16038748 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.73 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.66 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.65 |
Solubility | 0.0638 mg/ml ; 0.000226 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.62 |
Solubility | 0.0681 mg/ml ; 0.000242 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.11 |
Solubility | 0.221 mg/ml ; 0.000783 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) |
Yes |
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 |
-6.08 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 |
3.0 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 |
---|---|---|
70% | With methanol; In tetrahydrofuran; at 20℃; for 2h; | To a solution of compound S1 (2 g, 7.11 mmol) in THF (15 mL) was added MeONa/MeOH solution (1.2 mL, 6.05 mmol, 1.3 M). The reaction was stirred at room temperature for 2 hrs and quenched with water. The resulting mixture was extracted with EtOAc twice. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was purified by silica gel column eluted with (PE/Acetone=30/1) to give the title compound (1.45 g, 70% yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Methanol (1.48 g, 46.1 mmol) is slowly added to a cooled suspension (00C) of NaH (2.12 g, 53.2 mmol, 60% dispersion in mineral oil, washed with hexane prior to <n="85"/>use) in THF (20 ml_). Upon completion of the addition the mixture is stirred at 00C for 150 min before 2,6-dibromo-4-nitropyridine (10.0 g, 35.4 mmol) is added. The temperature rises to 14C. The mixture is stirred at rt for 3 h before the reaction is quenched with sat. aq. NH4CI solution. The mixture is diluted with water and extracted twice with EA (250 ml_). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with DCM to give 2,6-dibromo-4-methoxy-pyridine (6.43 g) as an off-white solid; LC-MS: tR = 0.90 min, [M+1]+ = 267.75. | ||
a) Methanol (1.48 g, 46.1 mmol) is slowly added to a cooled suspension (0 C.) of NaH (2.12 g, 53.2 mmol, 60% dispersion in mineral oil, washed with hexane prior to use) in THF (20 mL). Upon completion of the addition the mixture is stirred at 0 C. for 150 min before 2,6-dibromo-4-nitropyridine (10.0 g, 35.4 mmol) is added. The temperature rises to 14 C. The mixture is stirred at rt for 3 h before the reaction is quenched with sat. aq. NH4Cl solution. The mixture is diluted with water and extracted twice with EA (250 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with DCM to give 2,6-dibromo-4-methoxy-pyridine (6.43 g) as an off-white solid; LC-MS: tR=0.90 min, [M+1]+=267.75. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; methanol; mineral oil; | (1) Production of 2,6-dibromo-4-methoxy pyridine as an intermediate product 1.49 g (ca. 60% in mineral oil; 0.0355*1.05 mol) of sodium hydride was washed with hexane and suspended in tetrahydrofuran. The suspension was mixed with 1.70 g (0.0355*1.5 mol) of methanol and then with 10.00 g (0.0355 mol) of 2,6-dibromo-4-nitropyridine, and stirred at room temperature for about one hour. Further, the suspension was mixed with 0.2 g (ca. 60% in mineral oil; 0.0355*0.14 mol) of sodium hydride, and stirred for about one hour. Next, 1.0 g (0.0355*0.9 mol) of methanol was added to the suspension, and after it was determined that no foaming was caused therein, the reaction solution was distributed with ethyl acetate-saturated sodium bicarbonate water. The organic phase of the obtained reaction solution was washed with saturated brine, dried with anhydrous sodium sulfate and then concentrated, thereby obtaining an aimed product. Yield by weight: 9.27 g; yield by percentage: 98%; solid; melting point: 131 to 133 C.; 1 H-NMR (60 MHz, CDCl3, delta): 3.79 (3H, s), 6.89 (2H, s). | |
In tetrahydrofuran; methanol; mineral oil; | (1) Synthesis of an Intermediate, 2,6-dibromo-4-methoxypyridine Sodium hydride (1.49 g (ca.60% in mineral oil), 0.0355*1.05 mol) was washed with hexane and suspended in tetrahydrofuran, and methanol (1.70 g, 0.0355*1.5 mol) was added thereto. Then, 2,6-dibromo-4-nitropyridine (10.00 g, 0.0355 mol) was added thereto and the resultant solution was stirred for about 1 hour at room temperature. Additional sodium hydride (0.2 g (Ca.60% in mineral oil), 0.0355*0.14 mol) was added, then the resultant solution was stirred for about 1 hour. After it was confirmed that there was no bubbling with the addition of methanol (1.0 g, 0.0355*0.9 mol), the reaction solution was partitioned between ethyl acetate and aqueous saturated sodium hydrogen carbonate. The obtained organic layer was washed with aqueous saturated sodium chloride, dried over anhydrous sodium sutfate and thereafter concentrated to obtain the end product. Yield: 9.27 g (98%). Solid. Melting point: 131 to 133 C. 1 H-NMR (60 MHz, CDCl3, delta): 3.79(3H, s), 6.89(2H, s). |
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