Structure of 105170-27-2
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 105170-27-2 |
Formula : | C6H6BrNO |
M.W : | 188.02 |
SMILES Code : | BrC1=NC=C(C=C1)OC |
MDL No. : | MFCD07781221 |
InChI Key : | WULVUFYZVYHTFX-UHFFFAOYSA-N |
Pubchem ID : | 11148151 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.43 |
TPSA ? Topological Polar Surface Area: Calculated from |
22.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.01 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.85 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.92 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.74 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.6 |
Solubility | 0.474 mg/ml ; 0.00252 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.94 |
Solubility | 2.18 mg/ml ; 0.0116 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.185 mg/ml ; 0.000986 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 |
-6.13 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 |
1.0 |
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<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 |
---|---|---|
63% | With sodium hydroxide; bromine; sodium nitrite; In water; hydrogen bromide; | (a) <strong>[10167-97-2]2-Amino-5-methoxypyridine</strong> (14.8 g, prepared by the method of J.G. Lombardino, J. Med. Chem., 1981, 24, 39) was dissolved in 60percent hydrobromic acid (150 ml) and to the cooled (-10°) stirred solution bromine (47.47 g) was added dropwise. To the resulting yellow suspension was added, dropwise, sodium nitrite (20.53 g) in water (40 ml), keeping the temperature below -5°. The mixture was stirred to room temperature, and after 0.5 hour cooled to 0°, and a solution of sodium hydroxide (120 g) in water (100 ml) was slowly added. The mixture was thoroughly extracted with ether, the combined ether extracts dried with anhydrous sodium sulphate, and evaporated. The residue was chromatographed on silica gel (150 g). Elution with dichloromethane gave a yellow oil (14.1 g, 63percent) which was combined with a smaller batch (3.4 g) and distilled under reduced pressure to give 2-bromo-5-methoxypyridine (16.4 g). b.p. 76°-78°/0.6 torr. |
63% | With sodium hydroxide; bromine; sodium nitrite; In water; hydrogen bromide; | (a) <strong>[10167-97-2]2-Amino-5-methoxypyridine</strong> (14.8 g, prepared by the method of J.G. Lombardino, J. Med. Chem. , 1981, 24 , 39) was dissolved in 60percent hydrobromic acid (150 ml) and to the cooled (-10°) stirred solution bromine (47.47 g) was added dropwise. To the resulting yellow suspension was added, dropwise, sodium nitrite (20.53 g) in water (40 ml), keeping the temperature below -5°. The mixture was stirred to room temperature, and after 0.5 hour cooled to 0°, and a solution of sodium hydroxide (120 g) in water (100 ml) was slowly added. The mixture was thoroughly extracted with ether, the combined ether extracts dried with anhydrous sodium sulphate, and evaporated. The residue was chromatographed on silica gel (150 g). Elution with dichloromethane gave a yellow oil (14.1 g, 63percent) which was combined with a smaller batch (3.4 g) and distilled under reduced pressure to give 2-bromo-5-methoxypyridine (16.4 g). b.p. 76-78°/0.6 torr. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate; sodium carbonate; triphenylphosphine; In propan-1-ol; water; at 95.0℃;Inert atmosphere; | In a 4 mL vial, palladium acetate (4.9 mg, 0.022 mmol), triphenylphosphine (12.1 mg, 0.046 mmol), 2M aqueous solution of sodium carbonate (0.96 ml, 1.920 mmol) and water (0.3 ml, 16.65 mmol) were successively added to a mixture of 2-bromo-5-methoxypyridine (0.1 ml, 0.814 mmol) and <strong>[871329-84-9]3-carboxy-5-fluorophenylboronic acid</strong> (148 mg, 0.805 mmol) in 1-propanol (1.5 ml, 19.97 mmol) under nitrogen. The mixture was stirred at 95 C overnight. The mixture was quenched with IN HCl and the product was extracted three times with AcOEt. The aqueous phase was neutralized to pH 7 with NaOH 10% and extracted twice with AcOEt. The combined organic layers were washed once with water, once with brine, dried over anh. Na2SO4 and concentrated. The white solid in suspension in aqueous phase was filtrated and the two products were mixed together to give the title material as a white solid used as is. LC (Method B): 1.747 min. 1H NMR (400 MHz, acetone) δ ppm 8.54 - 8.58 (m, 1H) 8.41 (dd, J=3.1, 0.8 Hz, 1H) 8.07 (ddd, J=10.3, 2.7, 1.7 Hz,1H) 8.03 (dd, J=9.0, 0.8 Hz,1H) 7.69 (ddd, J=9.0, 2.6, 1.4 Hz, 1H) 7.50 (dd, J=8.8, 2.9 Hz, 1H) 3.96 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; at 120℃; | General procedure: A mixture of methyl anthranilate (50 mg, 1 equiv.), 2-bromopyridine (2 equiv.),Pd(OAc)2 (0.03 equiv.), Xantphos (0.04 equiv.), and Cs2CO3 (2.5 equiv.) in eucalyptol(1.5 mL) was stirred at 120 C for 18-24 h. The reaction was followed by TLC. After completion,the reaction was then cooled to room temperature, and the mixture was concentratedunder vacuum. The solid obtained was purified by flash chromatography using a mixtureof ethyl acetate/petroleum ether. |
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