Structure of 115029-23-7
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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. : | 115029-23-7 |
Formula : | C8H4F4O2 |
M.W : | 208.11 |
SMILES Code : | O=C(O)C1=CC(C(F)(F)F)=CC=C1F |
MDL No. : | MFCD00061292 |
Boiling Point : | No data available |
InChI Key : | LIFKXWNFWIUMJT-UHFFFAOYSA-N |
Pubchem ID : | 688292 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.36 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 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 |
3.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.09 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.87 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.33 |
Solubility | 0.097 mg/ml ; 0.000466 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.66 |
Solubility | 0.046 mg/ml ; 0.000221 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.94 |
Solubility | 0.237 mg/ml ; 0.00114 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 |
-5.3 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 |
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) |
1.62 |
* 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 |
---|---|---|
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 4h; | General procedure: To a suspension of the carboxylic acid (5.00 mmol) in CH2Cl2 (15 mL) was added DMF (2 drops) followed by oxalylchloride (0.530 mL, 6.25 mmol). The reaction mixture was stirred at rt for 4 h, and then evaporated to dryness. Theacid chloride thus prepared was dissolved in CH2Cl2 (15 mL) at 0 C. Triethylamine (2.10 mL, 15.0 mmol) and added,followed by either ethylamine hydrochloride, benzylamine, or 2,4-dimethoxybenzylamine (7.50 mmol). The reactionmixture was allowed to warm to rt and stirred for a further 15 h. Water (50 mL) was added, and the aqueous phaseextracted with CH2Cl2 (3 × 50 mL). The combined organics were washed with saturated Na2CO3 (20 mL), dried overMgSO4, subjected to filtration, and concentrated in vacuo. The crude product was purified by flash chromatographyon silica gel, eluting with EtOAc/hexanes/CH2Cl2, to afford the title compound. | |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 3h;Inert atmosphere; | To a solution of 2-fluoro-5-trifluoromethylbenzoic acid (500 mg, 2.4 mmol) in anhydrous dichloromethane (10 mL) was added oxalyl chloride (410 μL, 4.8 mmol) followed by N,N-dimethylformamide (2 drops) and the mixture was stirred at room temperature for 3 hours. The volatiles were removed under a stream of nitrogen and the residue taken up in dichloromethane and added slowly to a solution of 11 (540 mg, 2.4 mmol) and N,N-diisopropylethylamine (1.0 mL, 6.0 mmol) in dichloromethane (10 mL) at 0 C. The mixture was warmed to room temperature and stirred for 4 hours. The mixture was diluted with dichloromethane (30 mL) and washed with saturated aqueous sodium hydrogen carbonate (20 mL) and saturated aqueous ammonium chloride. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and purified by flash column chromatography using ethyl acetate, hexane (0:1 to 3:7) as an eluent to obtain the title compound (660 mg, 67%) as an off-white waxy solid, Rf: 0.45 (2:3 ethyl acetate, hexane); IR (vmax (neat)): 3294, 2962, 1680, 1547, 1326, 1232, 1129, 1092 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.31 (9H, s), 1.62-1.76 (2H, m), 1.80-1.94 (1H, m), 2.00-2.08 (1H, m), 3.68-3.89 (2H, m), 4.11 (1H, dd, J = 15.1, 5.8 Hz), 4.18-4.29 (1H, m), 4.41 (1H, dd, J = 15.4, 1.9 Hz), 6.55 (1H, s), 7.28-7.36 (1H, m), 7.74-7.84 (1H, m), 8.39 (1H, dd, J = 6.9, 2.5 Hz), 10.08 (1H, d, J = 8.1 Hz) ppm; 13C NMR (100 MHz, CDCl3): δ 25.9, 28.1, 30.6, 32.4, 53.0, 68.8, 79.7, 95.6, 117.3 (d, J = 25.3 Hz), 122.4 (d, J = 13.8 Hz), 122.9 (q, J = 272.1 Hz), 128.0 (q, J = 30.3 Hz), 130.1-130.2 (m), 130.7-140.0 (m), 136.4, 159.0 (d, J = 2.8 Hz), 161.0, 161.9 (d, J = 255.2 Hz) ppm; 19F NMR (282 MHz, DMSO-d6): δ -62.3 (CF3), -108.4 (CF) ppm; LRMS (+ESI) m/z: 436.2 ([M+Na]+ 100%), 849.2 ([2M+Na]+ 43%). | |
With thionyl chloride; at 80℃; for 16h;Inert atmosphere; | 2-Fluoro-5-(trifluoromethyl)benzoic acid 7a (382 mg, 1.83 mmol, Shanghai Bide Pharmatech Ltd.) was added to thionyl chloride (5 mL), and the reaction solution was reacted at 80C for 16 hours. The reaction solution was concentrated to obtain the crude title compound 7b (400 mg), which was used directly in the next step without purification. |
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