Structure of 827614-70-0
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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. : | 827614-70-0 |
Formula : | C12H14BF3O2 |
M.W : | 258.04 |
SMILES Code : | CC1(C)OB(OC1(C)C)C1=CC(F)=C(F)C(F)=C1 |
MDL No. : | MFCD05663885 |
InChI Key : | VFCTUUBAONBDJU-UHFFFAOYSA-N |
Pubchem ID : | 2760701 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 62.79 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.66 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.64 |
Solubility | 0.0587 mg/ml ; 0.000228 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.27 |
Solubility | 0.139 mg/ml ; 0.000537 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.84 |
Solubility | 0.00375 mg/ml ; 0.0000145 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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) |
Yes |
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 |
-5.59 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 |
2.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.01 |
* 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 ethanol; at 20℃; for 0.5h; | General procedure: General procedure: The synthetic procedure for pentafluorophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonate (a) is presented as an example (Scheme 1). 2,2'-Bis(1,3,2-benzodioxaborole) (cat2B2, 262 mg, 1.10 mmol), PdCl2(dppf) (25 mg, 0.030 mmol), AcOK (294 mg, 3.0 mmol), pentafluorophenyl 4-bromobenzenesulfonate (403 mg, 1.0 mmol), and EtOH (6.0 mL) were charged in a reaction vessel under an Ar atmosphere. The resulting mixture was stirred for 2 h at 80 C. After cooling to room temperature, pinacol (260 mg, 2.20 mmol) was added to the mixture. The mixture was further stirred for 30 min at room temperature. H2O and n-hexane were added to the mixture and the product was extracted into the organic layer. After drying the organic layer with anhydrous MgSO4, solids were removed by filtration. The filtrate was concentrated. The product was obtained as a white solid by Kugelrohr distillation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: 2.5 eq. of the appropriate boronic acid was dissolved in dry dioxane (5 mL/mmol Preparation 25), then 2.5 eq pinaeol and dry acidic Amberlyst (100 mg/mmol boronie acid) were added and the mixture was stined at room temperature overnight, then it was filtered (if the appropriate boronic ester was available, then it was dissolved in dioxane (5 mL /rmnol Preparation 25) and this solution was used instead of the filtrate). 1 eq. ethyl(2B)-2-[(5S0)-5-(3 -ehloro-4-hydroxy-2-methyl-phenyl)-6-iodo-thieno[2,3-d]pyrimidin-4-yl]oxy-3-(2-methoxyphenyl)propanoate (Preparation 25), 0.1 eq. PdC12 x dppf, 2.5 eq. Cs2CO3 and water (2.5 mL/mmol) were added to the filtrate and the mixture was heated under nitrogen at 110C in a microwave reactor until no further conversion was observed. Then it was diluted with brine, neutralized with 2 M HCI, and extracted with DCM. Thecombined organic phases were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified via flash chromatography using heptane and EtOAc as eluents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.2% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 85℃;Inert atmosphere; | Under a nitrogen atmosphere, Add 2.52 g (12 mmol) to a 250 ml three-neck round bottom reaction flask4-bromo-3,5-dimethylbenzonitrile and 2.814 g (16 mmol) of 4,4,5,5-tetramethyl-2-(3,4,5-trifluorophenyl)-1,3, 2-dioxaborolan,Then, 120 ml of toluene, 50 ml of ethanol was added, and then 40 ml of a saturated solution of potassium carbonate (2 mol/L) was added and stirred. After 15 minutes of aeration, tetrakis(triphenylphosphine)palladium 100 mg (0.087 mmol) was added and aeration was continued for 15 minutes. The reaction system was heated to 85 C and stirred at reflux overnight.After the reaction was stopped to return to room temperature, the solvent of the reaction system was removed by rotary evaporation. The reaction system was extracted with dichloromethane and washed three times with deionized water and three times with brine.The product was purified by column chromatography using a mixture of petroleum ether and dichloromethane in a ratio of 3:1.Finally, 2.8 g of a white solid 3',4',5'-trifluoro-2,6-dimethyl-[1,1'-biphenyl]-4-carbonitrile (intermediate product) was obtained.The yield was 89.2%. |
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