Structure of 57381-39-2
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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. : | 57381-39-2 |
Formula : | C7H3BrFN |
M.W : | 200.01 |
SMILES Code : | C1=C(C(=CC=C1F)Br)C#N |
MDL No. : | MFCD00142875 |
InChI Key : | MDHNVHCZDCSTMS-UHFFFAOYSA-N |
Pubchem ID : | 93654 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P280 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 38.81 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.88 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.63 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.05 |
Solubility | 0.176 mg/ml ; 0.000881 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.57 |
Solubility | 0.535 mg/ml ; 0.00268 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.62 |
Solubility | 0.0481 mg/ml ; 0.00024 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 |
-5.79 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) |
1.67 |
* 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 potassium fluoride;tris(dibenzylideneacetone)dipalladium (0); In tetrahydrofuran; 2-Methylpentane; water; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; ethyl acetate; | 5'-Acetyl-4,2'-difluorobiphenyl-2-carbonitrile To a degassed solution of 1-[4-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]ethanone (12 g, 45.43 mmol), 2-bromo-5-fluorobenzonitrile (9.09 g, 5.28 ml, 45.44 mmol), potassium fluoride (7.92 g, 136.31 mmol) and tris(dibenzylideneacetone)palladium(0) (0.834 g, 0.908 mmol) in THF (200 ml) and water (10 ml) was added tri-tert butylphosphine (10% weight solution) (0.368 g, 3.63 ml, 1.817 mmol). The reaction was heated at 70 C. for 14 h then allowed to cool to ambient temperature. The reaction was partitioned between water (200 ml) and ether (300 ml). The aqueous phase was extracted with ether (150 ml) and the combined organics washed with brine (200 ml), dried (MgSO4), filtered and evaporated to give a brown solid. The solid was dissolved in DCM and adsorbed onto silica. The crude product was chromatographed on silica (5-20% EtOAc in isohexane) to give the title product as a white solid (6.8 g): δH (400 MHz, CDCl3) 2.63 (3H, s), 7.31 (1H, t, J 9.0 Hz), 7.40-7.44 (1H, m), 7.50-7.53 (2H, m), 8.02-8.10 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | 33a 33bTo a solution of 2-bromo-5-fluoro-benzonitrile 33a (10 g, 50 mmol) in dry tetrahydrofuran (100 mL) under nitrogen was added methylmagnesium bromide (3.2 M in ether, 19 mL, 60.0 mmol), and the resulting mixture was heated to reflux for 4 hours. The RM was then cooled down to RT, poured into a 2 N HCl solution (100 mL) and then diluted with methanol (100 mL). The resulting green solution was concentrated on a steam bath for 1 h at which point the organic solvents had been removed and the crude product had precipitated. The reaction mixture was then extracted with ethyl acetate, dried over MgSO4 and concentrated. The residue was purified by column chromatography using heptane and dichloromethane to give 4.88 g (45% yield) of the desired product l-(2-bromo-5-fluorophenyl)ethanone 33b as a pink oil; m/z 218 [M+H]+. | |
45% | In tetrahydrofuran; diethyl ether; for 4h;Inert atmosphere; Reflux; | To a solution of 2-bromo-5-fluorobenzonitrile (10.0 g, 48.5 mmol) in anhydrous tetrahydrofuran (100 mL) under nitrogen was added methylmagnesium bromide (3.2M in ether, 19 mL, 60.0 mmol). The resulting mixture was heated to reflux for 4 h. The reaction mixture was then cooled, poured into 2N hydrochloric acid (100 mL), and diluted with methanol (100 mL). The organic solvents were removed and the crude product precipitated out. The reaction mixture was extracted with ethyl acetate, dried over MgS04, and concentrated. The residue was purified by column chromatography (heptane/dichloromethane) to give 4.88 g (21.9 mmol, 45percent) of compound 86 as a pink oil. |
45% | In tetrahydrofuran; diethyl ether; for 4h;Reflux; | To a solution of 2-bromo-5-fluorobenzonitrile (10.0 g, 48.5 mmol) in anhydrous tetrahydrofuran (100 mL) under nitrogen was added methylmagnesium bromide (3.2M in ether,19 mL, 60.0 mmol). The resulting mixture was heated to reflux for 4 h. The reaction mixture was then cooled, poured into 2N hydrochloric acid (100 mL), and diluted with methanol (100 mL). The organic solvents were removed and the crude product precipitated out. The reaction mixture was extracted with ethyl acetate, dried over MgSO4, and concentrated. The residue was purified by column chromatography (heptane/dichioromethane) to give 4.88 g (21.9 mmol, 45percent)of compound 86 as a pink oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.5% | With sodium tetrahydroborate; trifluoroacetic acid; In tetrahydrofuran; at 20℃; for 16h; | To a solution of 2-bromo-5-fluorobenzonitrile (3.0g, 15.00mmol) and NaBH4 (1.419 g, 37.5 mmol) in THF (30mL) was slowly added TFA (3.47 ml., 45.0 mmol) over a period of20 min. The resulting mixture was stirred at rt for 16 hours, then MeOH (10 mL) was added and the mixture wasstirred for another 30 min. It was then diluted with EtOAc(200 ml.), washed with water, dried over Na2S04 and evaporated.The residue was purified on an 80 g Thompson silicacartridge (3% to 100% B in Hexanes, 1200 ml., B: 10%MeOH in EtOAc). The desired product was obtained as acolorless oil (1.70 g, 8.33 mmol, 55.5% yield). |
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