Structure of 19346-46-4
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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. : | 19346-46-4 |
Formula : | C6H5FN2O2 |
M.W : | 156.11 |
SMILES Code : | O=[N+](C1=CN=C(F)C(C)=C1)[O-] |
MDL No. : | MFCD03095069 |
InChI Key : | CFKHKTLGKNBEPI-UHFFFAOYSA-N |
Pubchem ID : | 12408184 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 37.98 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.86 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.1 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.08 |
Solubility | 1.3 mg/ml ; 0.00836 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.32 |
Solubility | 0.747 mg/ml ; 0.00479 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.06 |
Solubility | 1.37 mg/ml ; 0.00875 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 |
-6.2 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 |
3.0 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) |
2.05 |
* 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 |
---|---|---|
15% | With N-Bromosuccinimide; In dichloromethane; at 20℃; for 48h; | 3-Bromomethyl-2-fluoro-5-nitro-pyridine:; 2-Fluoro-3-methyl-5-nitro-pyridine (445 mg, 2.85 mmol) was dissolved in 20 mL DCM. NBS (1.01 g, 5.7 mmol, 2 eq.) was added. The reaction was stirred at room temperature for 2 days. HPLC showed 20% conversion. The reaction was concentrated down and purified (silica gel, 0-80% EtOAc/hexane) to give light yellow oil (100 mg, 15%). 1H NMR (300 MHz, CD3OD): delta 8.39 (m, 2H), 7.61 (m, 1H), 4.86 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With KF; In hexane; acetonitrile; | 18a. 2-fluoro-3-methyl-5-nitropyridine 2-Chloro-3-methyl-5-nitropyridine (15 g, 86.9 mmol; from Maybridge Chemical Co.), KF (12 g, 258 mmol) and tetraphenylphosphonium bromide (20 g, 47.7 mmol; Aldrich) were combined in 200 mL of acetonitrile and heated at reflux for 4 days. The mixture was diluted with Et2 O (500 mL) and filtered, and the filtrate was concentrated. The residue was triturated with hot hexane (4*200 mL), and the hexane solutions were combined and concentrated to afford the title compound as a solid (8.4 g, 60%): 1 H NMR (DMSO-d6, 300 MHz) delta2.42 (s, 3H), 8.43 (m, 1H), 8.95 (dd, J=1.6 Hz, 1H); MS (CI/NH3) m/z: 157 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | palladium-carbon; In ethanol; | 18b. 5-amino-2-fluoro-3-methylpyridine <strong>[19346-46-4]2-Fluoro-3-methyl-5-nitropyridine</strong> (8.2 g, mmol) was combined with 5% Pd/C (100 mg) in EtOH (100 mL) under a H2 atmosphere for 16 hours. The mixture was filtered and concentrated, and the crude product was chromatographed (silica gel; CHCl3 /MeOH 99:1 to 96:4) to afford a solid (5.2 g, 78%): 1 H NMR (DMSO-d6, 300 MHz) delta2.10 (s, 3H), 5.11 (brs, 2H), 6.95 (dd, J=8.14 Hz, 1H), 7.26 (t, J=2.72 Hz, 1H); MS (CI/NH3) m/z: 127 (M+H)+, 144 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | Sodium hydride (1.54 g of 60 % dispersion in oil, 38.5 mmol, 2 eq) was added to a solution of cyanoacetone sodium salt (2.5 g, 23 mmol, 1.2 eq) in DMF (40 mL) at RT. The mixture was stirred for 15 min, then a solution of 2-fluoro-3-methyl-5- nitropyridine (3.0 g, 19.2 mmol, 1.0 eq) in 10 mL DMF was added dropwise. The reaction mixture was stirred at RT for 6 hr. The reaction was quenched with 5 g ice, followed by 150 mL water and 10 mL acetic acid. The mixture was extracted with ethyl acetate, then the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 30% ethyl acetate in hexanes as eluent, providing 11 a (1.85 g, 44 % yield) as an orange oil. | |
44% | Sodium hydride (1.54 g of 60 % dispersion in oil, 38.5 mmol, 2 eq) was added to a solution of cyanoacetone sodium salt (2.5 g, 23 mmol, 1.2 eq) in DMF (40 mL) at rt. The mixture was stirred for 15 min, then a solution of 2-fluoro-3- methyl-5-nitropyridine (3.0 g, 19.2 mmol, 1.0 eq) in 10 mL DMF was added dropwise. The reaction mixture was stirred at rt for 6 h. The reaction was quenched with 5 g ice, followed by 150 mL water and 10 mL acetic acid. The mixture was extracted with ethyl acetate, then the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 30% ethyl acetate in hexanes as eluant, providing 13a (1.85 g, 44 % yield) as an orange oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20 - 60℃; | General procedure: The synthesis of 3-methyl-5-nitro-2-(2-phenylhydrazinyl)pyridine (PH5N3M) was performed in the following way: 0.01 mol of <strong>[19346-46-4]2-fluoro-3-methyl-5-nitropyridine</strong> was dissolved in10 cm3 of methanol and 0.02 mol of phenylhydrazine was added to this solution. The obtained mixture was heated for 1-2 min at 60 C and left at room temperature for 24 h. Next, the solvent was distilled off under reduced pressure and the residue was extracted with hot chloroform. Insoluble hydrofluoride phenylhydrazine was filtered and washed with warm chloroform. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; at 20℃; for 16h; | Potassium Carbonate was added to a solution of 5-bromobenzene-1,3-diol and <strong>[19346-46-4]2-fluoro-3-methyl-5-nitropyridine</strong> and stirred at room temperature for 16 hours. Reaction mixture was diluted with ice cold water and extracted with ethyl acetate. The combined organic layer was dried with sodium sulphate and evaporated under reduced pressure to obtain 2,2'-(5-bromo-1,3-phenylene)bis(oxy)bis(3-methyl-5-nitropyridine). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h; | Potassium Carbonate was added to a solution of benzene-1, 3, 5-triol and 2-fluoro-3, 6-dimethyl-5-nitropyridine in dimethyl form amide and the reaction mixture was stirred at room temperature for 16 h. Reaction mixture was diluted with ice cold water and extracted with ethyl acetate. The combined organic layer was dried with sodium sulphate and evaporated under reduced pressure to obtain 1,3,5-tris(3-methyl-5-nitropyridin-2-yloxy)benzene. |
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