Structure of 71682-97-8
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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. : | 71682-97-8 |
Formula : | C9H5F2NO |
M.W : | 181.14 |
SMILES Code : | N#CCC(C1=CC=C(F)C(F)=C1)=O |
MDL No. : | MFCD02260781 |
InChI Key : | DMUDJKIYVPYJNF-UHFFFAOYSA-N |
Pubchem ID : | 2758254 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.86 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.4 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.99 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.9 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.92 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.22 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.43 |
Solubility | 0.679 mg/ml ; 0.00375 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.47 |
Solubility | 0.608 mg/ml ; 0.00336 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.4 |
Solubility | 0.0729 mg/ml ; 0.000403 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 |
-5.99 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 |
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) |
1.48 |
* 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 dichloromethane; water; | EXAMPLE 55 2-(3,4-Difluorobenzoyl)-3-hydroxycrotononitrile A solution of 10.2 g. of <strong>[71682-97-8]3,4-difluorobenzoylacetonitrile</strong>, 9.2 g. of triethyl orthoacetate and 20 ml. of acetic anhyride is heated on a steam bath for 0.5 hour and then poured into 200 ml. of water which is then heated on the steam bath for 2 hours. On cooling, the solid is filtered and then dissolved in methylene chloride. This solution is extracted with two portions of aqueous sodium bicarbonate and the aqueous extracts are combined and acidified with concentrated hydrochloric acid. The precipitate is extracted into methylene chloride, passed through a pad of Magnesol.(R)., heated and diluted with hexane. Upon cooling, colorless crystals result, yielding the title compound, m.p. 51°-54° C. Similarly prepared are 2-(2,5-difluorobenzoyl)-3-hydroxycrotononitrile, 2-(3,4,5-trimethoxybenzoyl)-3-hydroxycrotononitrile, 2-(2,4,6-trimethylbenzoyl)-3-hydroxycrotononitrile, and 2-(2,5-dichlorobenzoyl)-3-hydroxycrotononitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrachloromethane; ethanol; water; | EXAMPLE 5 3,4-difluorobenzoylacetonitrile A solution of 13.2 g. (0.056 mole) of 3,4-difluorophenacyl bromide was dissolved in 100 ml. of ethanol and cooled to 5° C. in ice. A solution of 7.6 g. (0.16 mole) of sodium cyanide in 40 ml. of water was added dropwise over 0.5 hr. and the reaction is stirred for an additional one hour. At that time, the mixture was diluted with 100 ml. of water and filtered through Celite.(R).. Acidification of the filtrate gave a cloudy mixture which was extracted with methylene chloride. The organic phase was dried, filtered through Magnesol.(R). and evaporated. Recrystallization of the residue from carbon tetrachloride provides 5.3 g. (52percent) of colorless solid, m.p. 74°-75° C. Similarly prepared were 2,4-dichlorobenzoylacetonitrile, o-ethylbenzoylacetonitrile, p-isopropylbenzoylacetonitrile, m-isobutylbenzoylacetonitrile, 3,4-dimethylbenzoylacetonitrile, m-ethoxybenzoylacetonitrile, p-isopropoxybenzoylacetonitrile, 3,4-diethoxybenzoylacetonitrile, and 2,5-difluorobenzoylacetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In neat (no solvent); at 130℃; for 1.5h; | [0531] A thoroughly mixed mixture of 3-ethyl 4-methyl 2-hydrazinylthiophene-3 ,4- dicarboxylate (0.3 g, 1.228 mmol, 1 eq) and <strong>[71682-97-8]3-(3,4-difluorophenyl)-3-oxopropanenitrile</strong> (0.222 g, 1.228 mmol, 1 eq) in an open vial was stirred neat at 130 °C for 1.5 h. The melted liquid becomes thick solid which is triturated in DCM/MeOH. The crude product was purified on flash system using a 24 g silica column eluting with 1-10 percent methanol in DCM over 12 column volumes. The pure fraction was pooled and concentrated to get 0.49 g (Yield = 84 percent) of white solid. |
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