Structure of 179062-06-7
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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. : | 179062-06-7 |
Formula : | C7H6F4N2 |
M.W : | 194.13 |
SMILES Code : | NC1=CC(C(F)(F)F)=C(F)C=C1N |
MDL No. : | MFCD04038250 |
InChI Key : | WMKGEQCSIZQIEK-UHFFFAOYSA-N |
Pubchem ID : | 2774460 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.6 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.29 |
Solubility | 0.997 mg/ml ; 0.00514 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.24 |
Solubility | 1.11 mg/ml ; 0.00573 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.85 |
Solubility | 0.275 mg/ml ; 0.00142 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 |
-6.39 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) |
1.44 |
* 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 |
---|---|---|
95% | palladium-carbon; In ethanol; | D. 3,4-Diamino-6-fluorobenzotrifluoride A mixture of 3-amino-6-fluoro-4-nitrobenzotrifluoride (328 mg, 1.45 mmol) and 10% Pd/C (50 mg) in ethanol (15 mL) was hydrogenated for 2 h at 25 C. under 25 psi H2. The catalyst was removed by filtration with celite and the solvent was removed by rota-evaporation to give 270 mg of 3,4-diamino-6-fluorobenzotrifluoride (95%) as a brown solid. 1 H NMR (CDCl3): delta3.432 (br, 4H), 6.469 (d, 1H, J=8.4 Hz); 6.860 (d, 1H, J=6.6 Hz). |
With tin(ll) chloride; In ethanol; at 65 - 70℃; | To a stirred solution of 11.35 g (50.6 mmol) of the nitroaniline 18a in 250 mL of ethanol was added 57.1 g (253 mmol) of tin (II) chloride dihydrate at room temperature. The reaction was heated at 65-70 C. for 45 minutes. The reaction was cooled and poured into 900 mL of ice water. It was basified to pH 8 with solid sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and evaporated to give 9.33 g of compound 19a as a dark red solid. Calcd for C7H6F4N4.H+=195; Found m/z=195. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogensulfite; In ethanol; for 40.0h;Heating / reflux; | To a mixture of 2.8 g (7.4 mmol) of compound 16 in 10 mL of NaHSO3 and 25 mL of ethanol was added 1.43 g (7.4 mmol) of compound 19a. The mixture was stirred under reflux for 40 h and concentrated. The residue was diluted with 60 mL of H2O and extracted with three 80 mL portions of ethyl acetate. The combined organic extracts were washed with 50 mL of brine and concentrated. The residue was purified by silica gel chromatography eluting with a gradient from 10 to 40% ethyl acetate in hexanes to give 1.1 g of compound 11c. Calcd m/z for C25H24BrF4N3O2.H+=556; found m/z=556. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hydrogenchloride; sodium hydroxide; | E. 6-Fluoro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione A mixture of <strong>[179062-06-7]3,4-diamino-6-fluorobenzotrifluoride</strong> (270 mg, 1.38 mmol) and oxalic acid dihydrate (200 mg, 1.60 mmol, used as received) in 4N HCl (5 mL) was refluxed at 120-5 C. for 3 h, then cooled to room temperature. The mixture was centrifuged and the liquid layer was removed. The yellow solid was washed twice with cold water (2*2 mL), collected by filtration, and dried at 60 C. under reduced pressure for 2 h, affording 152 mg of crude title compound (40%) as a light yellow powder. The crude compound was dissolved in 1N NaOH (4 mL) and filtered. The filtrate was acidified to pH=5, affording 138 mg of title compound as a yellow powder. Mp: 330-333 C. IR (KBr, cm-1) 3398, 3170, 2959, 1701, 1641, 1515; 1398. 1 H NMR (DMSO-d6): delta7.079 (d, 1H, J=11.4 Hz); 7.376 (d, 1H, J=5.1 Hz); 12.022 (s, 1H); 12.225 (s, 1H). HRMS: calcd for C9 H4 F4 N2 O2 (M+) m/z: 248.0208; found: 248.0220. |
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