Structure of 176694-36-3
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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. : | 176694-36-3 |
Formula : | C9H6F4O2 |
M.W : | 222.14 |
SMILES Code : | FC1=C(C=C(C(=O)OC)C=C1)C(F)(F)F |
MDL No. : | MFCD06203709 |
Boiling Point : | No data available |
InChI Key : | IRYBOHVMFKZODT-UHFFFAOYSA-N |
Pubchem ID : | 15285559 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 42.68 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.28 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.76 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.38 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.19 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.05 |
Solubility | 0.196 mg/ml ; 0.000883 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.97 |
Solubility | 0.239 mg/ml ; 0.00108 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.65 |
Solubility | 0.0501 mg/ml ; 0.000225 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) |
Yes |
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 |
-5.7 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 |
0.55 |
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) |
1.81 |
* 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 |
---|---|---|
In methanol; diethyl ether; dichloromethane; at 0℃; for 0.333333h; | To a solution of <strong>[67515-55-3]4-fluoro-3-(trifluoromethyl)benzoic acid</strong> Ia (1.04 g, 5 mmol) in DCM/MeOH (4: 1, 10 mL) at 0 0C was added drop-wise a solution OfTMSCHN2 (2.0 M <n="119"/>in ether, 2.6 mL, 5.1 mmol). The reaction mixture was stirred at 00C until the colorless solution started to turn light yellow and maintained its light yellow color. The reaction was stirred for an additional 20 minutes then a few drops of acetic acid was added to quench the last few drops OfTMS-CHN2 (the solution turns colorless from light yellow). The solvent was removed in vacuo to give a crude product which was used directly for next step. MS (ESI, M-HH+) = 223.0 | |
A solution of <strong>[67515-55-3]4-fluoro-3-(trifluoromethyl)benzoic acid</strong> (260 mg, 1.25 mmol, 1 eq) in MeOH (0.5 ml_) and CH2CI2 (2 ml_) was treated with TMSCHN2 (2M in hexanes, 0.85 ml_, 1.70 mmol, 1.4 eq) dropwise with stirring at room temperature. After the reaction was stirred for 10 min, acetic acid was added until the yellow color disappeared. The mixture was concentrated to afford methyl 4-fluoro-3- (trifluoromethyl)benzoate, which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; In methanol; | a Methyl 4-fluoro-3-trifluoromethylbenzoate 5 g of <strong>[67515-55-3]4-fluoro-3-trifluoromethylbenzoic acid</strong> and 9 ml of SOCl2 are stirred at 60 C. for 8 h in 50 ml of MeOH. The volatile constituents are then removed in vacuo and 5.1 g of a colorless oil are obtained, which is further employed without purification. Rf (EA/MeOH 10:1)=0.74 MS (DCl) 223 (M+H)+ | |
With thionyl chloride; In methanol; | a) Methyl 4-fluoro-3-trifluoromethylbenzoate 5 g of <strong>[67515-55-3]4-fluoro-3-trifluoromethylbenzoic acid</strong> and 9 ml SOCl2 were stirred in 50 ml of MeOH at 60 C for 8 h. The volatile constituents were then removed in vacuo to result in 5.1 g of a colorless oil, which was employed further without purification. Rf(EA/MeOH 10:1)=0.74 MS (DCI) 223 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sulfuric acid; for 5h;Reflux; | To a stirred solution of <strong>[67515-55-3]4-fluoro-3-(trifluoromethyl)benzoic acid</strong> (10.0 g, 48.1 mmol) in MeOH (100 mL) was added cone. H2S04 (4 mL, 73.4 mmol) in drops at ambient temperature and the mixture was refluxed for 5 hours. 200 mL of aqueous solution of NaHC03 was added to basified the mixture, and the resulted mixture was extracted with EA (100 mL X 3). The combined extracts were washed with brine (100 mL X 2), dried, concentrated to obtain the title product (9.4 g, yield: 88%) as a light yellow oil. 1H MR (400 MHz, CDC13) delta 8.33 (dd, J = 6.8, 1.6 Hz, 1H), 8.28 - 8.22 (m, 1H), 7.28 (t, 1H), 3.95 (s, 3H). |
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