Structure of 40360-44-9
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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. : | 40360-44-9 |
Formula : | C6H2Cl3NO2 |
M.W : | 226.44 |
SMILES Code : | O=C(O)C1=NC(Cl)=C(Cl)C=C1Cl |
MDL No. : | MFCD01086756 |
InChI Key : | TVMKSGXYTVKNRK-UHFFFAOYSA-N |
Pubchem ID : | 919593 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 46.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.93 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.67 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.39 |
Solubility | 0.0914 mg/ml ; 0.000404 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.65 |
Solubility | 0.0512 mg/ml ; 0.000226 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.25 |
Solubility | 0.126 mg/ml ; 0.000557 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 |
-5.6 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 |
0.56 |
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) |
1.86 |
* 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 |
---|---|---|
68% | Stage #1: at 30℃; Stage #2: With hydrogenchloride In water |
To a reaction flask containing 200 mL of boiling water was added 26.1 g (0.1 mol) of tetrapicolinic acid, 4.1 g (0.103 mol) of sodium hydroxide previously dissolved in 25 mL of water and 3.47g (0.105mol) of anhydrous hydrazine. The reaction mixture was stirred under reflux for 30 min. An additional 4.1g (0.103mol) of sodium hydroxide in 25 mL of water was slowly added to <n="113"/>the reaction mixture over a 25 minute period and the mixture refluxed for 45 min. The reaction mixture was cooled to room temperature and 25 mL of 5N HCl was added. The solid 3,5,6- trichloro-4-hydrazinopicolinic acid (as the monohydrate) which precipitated was recovered by filtration in a yield of 22.9 g (83percent). Mp:166"-168°C. [00371] To a mixture (clear solution) of 3,5,6-tricWcro-4-hydrazinopicolinic acid (22.9 g, 78 mmol), 115 mL of2Qpercent sodium hydroxide and 15O mL of water was added 10O mL of 10-13percent sodium hypochlorite solution at 3O°C. Immediate gas evolution was noted which ceased after about 3 min. Five minutes after the addition of the sodium hypochlorite solution, the reaction mixture was acidified to a pH of about 2 with concentrated hydrochloric acid (15OmL). The mixture was extracted with methylene chloride. The methylene chloride was removed from the extract by evaporation leaving the crude 3,5,6-trichloropicolinic acid. The crude product was dissolved in IN NaOH to form a clear solution and cooled to 0 °C and neutralized with 5N HCl with stirring at O°C. The solid was filtered and washed with water to give the pure enough product (15.5 g, 88percent). Total yield: 68percent. Mp.l47-151°C. [00372] 1H NMR (DMSO^, 400 MHz): δ 14.31 (brs, 1H, OH, exchangeable with D2O), 8.60 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45.11% | With [2,2]bipyridinyl; nickel(II) chloride hexahydrate; sodium hydroxide; zinc In N,N-dimethyl-formamide at 20℃; Inert atmosphere | Three 8 mL scintillation vials were charged with NiC12•6H20 (12.0 mg, 0.05 1 mmol)and 2,2’-bipyridine (16.0 mg, 0.102 mmol). The vials were closed and purged with nitrogenfor 5 mm, after which the vials were charged with DMF (4.5 mL) and one of the following:deionized (DI) water (pH = 7), 10percent HC1, or 10percent sodium hydroxide (NaOH) (0.5 mL). The mixtures were allowed to stir for 5 mm. To each of the vials was added zinc dust (0.22 g, 3.4 mmol), and the mixtures were allowed to stir under nitrogen for 35 mm. Solid 3,4,5,6-tetrachloropicolinic acid (0.10 g, 0.4 mmol) was added to each through the top of the reactor. The reaction mixtures were allowed to stir at ambient temperature, and samples were removed periodically to determine reaction kinetics. The samples (—0.01 mL of reaction mixture diluted to 1.5 mL with acetonitrile) were analyzed by a calibrated HPLC method. |
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