Structure of 2,6-Difluorobenzaldehyde
CAS No.: 437-81-0
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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. : | 437-81-0 |
Formula : | C7H4F2O |
M.W : | 142.10 |
SMILES Code : | C1=CC=C(C(=C1F)C=O)F |
MDL No. : | MFCD00010293 |
InChI Key : | SOWRUJSGHKNOKN-UHFFFAOYSA-N |
Pubchem ID : | 136284 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H227-H315-H319-H335 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 31.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.58 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.32 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.82 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.14 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.09 |
Solubility | 1.14 mg/ml ; 0.00805 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 4.01 mg/ml ; 0.0282 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.88 |
Solubility | 0.188 mg/ml ; 0.00132 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 |
-6.05 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 |
2.0 |
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) |
1.0 |
* 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 |
---|---|---|
78.8% | In toluene;Reflux; | General procedure: The appropriate (hetero) aromatic amine (1.0 mmol) and 2',6'-/3',5'-dihalo-substituted (hetero/aromatic) aldehyde (1.5 mmol) were stirred in dry toluene under reflux condition followed by addition of mercaptoaceticacid (2.0 mmol). The reaction mixture was refluxed with a Dean-Stark trap for 24-48 h until the complete consumption of (hetero) aromatic amine. The reaction mixture was concentrated to dryness under reduced pressure and the residue was taken up in ethyl acetate. The organic layer was successively washed with 5percent aq citric acid, water, 5percent aq sodium hydrogen carbonate, and then finally with brine. The organic layer was dried over sodium sulfate and solvent was removed under reduced pressure to get a crude product that was purified by column chromatography on silica-gel (230-400 mesh) using hexane-ethyl acetate as eluent. The structures of synthesized compounds were characterized by means of TLC, IR, ESI-MS, 1H NMR, 13C NMR, elemental analyses and HRMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10%; 58% | General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82% yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil. |
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