Structure of 168971-68-4
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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. : | 168971-68-4 |
Formula : | C7H3BrF4O |
M.W : | 259.00 |
SMILES Code : | BrC1=C(C=C(C=C1)OC(F)(F)F)F |
MDL No. : | MFCD06657548 |
InChI Key : | KZMHSGBETSENAT-UHFFFAOYSA-N |
Pubchem ID : | 22065211 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362+P364-P403+P233-P501 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 40.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.4 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.89 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.11 |
Solubility | 0.0203 mg/ml ; 0.0000783 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.78 |
Solubility | 0.0428 mg/ml ; 0.000165 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.16 |
Solubility | 0.018 mg/ml ; 0.0000693 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) |
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 |
-5.12 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) |
1.87 |
* 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 |
---|---|---|
41% | With hydrogenchloride; n-butyllithium; In tetrahydrofuran; | Example I 2-Fluoro-4-trifluoromethoxybenzeneboronic Acid To a solution of n-butyllithium (2.5 M solution in hexanes, 14.1 mL) in THF (30 mL) at -98 C. was added a solution of 4-bromo-3-fluorotrifluoromethoxy-benzene in THF (3 mL). After stirring for 10 min. at -98 C., triisopropyl borate (4.88 mL, 3.98 g, 21 mmol) was added at a rate needed to keep the temperature below -97 C. The reaction mixture was allowed to warm to -30 C. over 30 minutes, re-cooled to -78 C. and stirred at this temperature for 30 min. Concentrated hydrochloric acid (2 mL) was added and the reaction mixture was concentrated under reduced pressure. Dilute hydrochloric acid (0.2 N, 15 mL) was added and the mixture was extracted with ether (3*20 mL). The combined ethereal layers were extracted with dilute sodium hydroxide (0.02 N, 3*30 mL). The combined aqueous extracts were cooled to 0 C., acidified to pH 3.5 using concentrated hydrochloric acid and extracted with ether (3*30 mL). The combined ethereal layers were then washed with water (15 mL) and brine (15 mL), dried over magnesium sulphate and concentrated under reduced pressure to leave 2.3 g of yellow solid. Recrystallisation from hexane afforded pink needles (1.25 g, 41%): mp 89-93 C.; 1H NMR (CDCl3) δ 7.89 (t, 1H), 7.07 (d, 1H), 6.94 (d, 1H), 5.11 (d, 2H); EI/MS 223 m/e (M-1). |
43 g | With n-butyllithium; In tetrahydrofuran; toluene; at -78 - -70℃; for 4h; | Tripropan-2-yl borate (43.6 g, 232 mmol) was added to a solution of 4-bromo-3-fluorophenyl trifluoromethyl ether (50.0 g, 193 mmol) in toluene (400 mL) and tetrahydrofuran (100 mL), and the mixture was cooled to -78 C. n-Butyllithium (2.5 M solution; 92.7 mL, 232 mmol) was then added drop-wise, at a rate that maintained the reaction temperature below -60 C., and the reaction mixture was stirred at -70 C. for 4 hours. After the reaction mixture had been warmed to -20 C., it was quenched via addition of aqueous hydrochloric acid (2 M, 200 mL), and then stirred at room temperature (20 C.) for 40 minutes. The aqueous layer was extracted with ethyl acetate (3×50 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the product (43 g) as a white solid, which was carried directly to the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.3 g | With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 110℃;Inert atmosphere; | General procedure: 5-Bromo-2-tert-butylpyridine (500 mg; 2.34 mmol) is dissolved in 5 ml_ of dioxane. Copper iodide (89 mg, 0.47 mmol) is added and the mixture is placed under argon atmosphere. Sodium iodide is added and the mixture is stirred for a few minutes under argon atmosphere. N,N?-dimethylethylenediamine (100 mI_, 0.93 mmol) is added and the mixture is stirred at 130C over night. The mixture is allowed to cool to room temperature before being diluted with ethyl acetate and extracted with saturated aqueous solution of sodium bicarbonate twice. The organic layer is dried over magnesium sulfate, filtered and concentrated.Yield: 610 mg (95 % of theory)Mass spectrometry (ESI+): m/z = 262 [M+H]+HPLC (Method 3): Retention time = 1.176 min. |
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