Structure of 4837-19-8
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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. : | 4837-19-8 |
Formula : | C8H6F2O3 |
M.W : | 188.13 |
SMILES Code : | O=C(O)C1=CC=CC(OC(F)F)=C1 |
MDL No. : | MFCD00236224 |
Boiling Point : | No data available |
InChI Key : | OKKDGIXOKWOMRD-UHFFFAOYSA-N |
Pubchem ID : | 842614 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 40.0 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.97 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.64 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.64 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.02 |
Solubility | 0.179 mg/ml ; 0.000953 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.61 |
Solubility | 0.0461 mg/ml ; 0.000245 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.12 |
Solubility | 1.43 mg/ml ; 0.00759 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 |
-5.34 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 |
0.56 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.5 |
* 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 |
---|---|---|
83% | To a solution of 3-(difluoromethoxy)benzoic acid (2.82 g, 15 mmol) in DCM (30 mL) was added Et3N (3.34 g, 33 mmol) followed by EDC (3.43 g, 18 mmol) and HOBt (0.27 g, 2 mmol) at room temperature. The reaction mixture was stirred at room temperature for 30 min. Then 0-(tert-butyl)-L- serine methyl ester hydrochloride (3.17 g, 15 mmol) was added and reaction mixture was stirred at room temperature for 12h. Evaporation of solvent under vacuum gave crude residue which was treated with saturated aqueous NaHC03 solution (10 mL), then extracted with ethyl acetate (2 x 100 mL). Dried (Na2S04), filtered and evaporation of solvent under vacuum gave almost pure product as pale yellow syrup which was used as such in the next. Yield : 4.33 g (83percent), LCMS m/z: 346.32 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; In acetonitrile; at 23℃; for 12h;Irradiation; Glovebox; Sealed tube; Inert atmosphere; | General procedure: In a glovebox, to an oven-dried 20 mL screw cap vial was added 1- (difluoromethoxy) -3-methyl-6-nitro-4- (trifluoromethyl) -lff- benzo [d] [1, 2, 3] triazol-3-ium trifluoromethanesulfonate (la) (92.4 mg, 0.200 mmol, 1.00 equiv), (hetero) arene (2.00 mmol, 10.0 equiv), Ru (bpy) 3 (PF6) 2, (0.860 mg, 1.00 pmol, 0.500 mol%), and MeCM (1.00 mL, 0.200 M, with respect to la) . To this suspension or solution was added a magnetic stir bar. Next, the reaction vial was capped and taken out of the glovebox. The reaction mixture was stirred at ambient temperature (23 C) and irradiated with blue LEDs (30 W, Xmax = 450 nm) which was placed 20.0 m from the vial for 12 h. To determine the yield of the products, an internal standard, trifluorotoluene (PhCF3) (14.6 mg, 12.3 pL, 0.100 mmol, 0.500 equiv) was added to the vial. Then, a 100 pL of the reaction mixture was taken and then dilute with 500 pL CD3CN followed by 19F NMR (the NMR sample was recombined with the rest of the reaction mixture afterward) . The combined reaction mixture was then purified by HPLC on the Luna PFP(2) preparative column (250 x 21.2 mm) column eluting with MeCN:H20 (v/v) with a flow rate of 10.6 mL/min to provide the purified products. In cases of closely-eluting peaks, products were isolated as a mixture of isomers. Afterwards, the products were extracted with CDC13 (3 x 1 mL) , dried with magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford the desired product (s). For very volatile compounds, the products were extracted immediately with CDCI3 (l x l mL) and then directly characterized. 1H and 13C NMR of these Compound (s) contains MeCN residue signal (1H NMR: □ 1.94, 13C NMR: u 118.26, 1.32 in CDCI3 ) |
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