Structure of 877131-92-5
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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. : | 877131-92-5 |
Formula : | C9H5BrF3N |
M.W : | 264.04 |
SMILES Code : | N#CCC1=CC=C(Br)C=C1C(F)(F)F |
MDL No. : | MFCD13185431 |
InChI Key : | DSDNDRQVAPPETF-UHFFFAOYSA-N |
Pubchem ID : | 58488407 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.67 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.69 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.85 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.46 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.65 |
Solubility | 0.0596 mg/ml ; 0.000226 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.32 |
Solubility | 0.127 mg/ml ; 0.000479 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.63 |
Solubility | 0.0062 mg/ml ; 0.0000235 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 |
-5.67 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.83 |
* 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 methanol; at 80.0℃; for 0.333333h;Microwave irradiation; | Step 2: r4-bromo-2-(trifluoromethyl)phenyH acetonitrile; A mixture of the benzyl bromide (1 eq.) from step 1 and KCN (1.1 eq.) in MeOH (0.32M) was subjected microwave (Smith Creator; Personal Chemistry),) for 20min at 8O0C. The mixture was cooled down to room temperature, concentrated and purification by column chromatography on silica gel, eluting with Hex/EtOAc 5%, afforded the title compound III.2 as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | To a stirred solution of <strong>[877131-92-5](4-bromo-2-trifluoromethyl-phenyl)-acetonitrile</strong> (3.33 g, 12.61 mmol) from step 2 of example A(141), benzyltriethylammoniym chloride (0.057 g, 0.25 mmol) and 1-bromo-2-chloroethane (1.57 g, 10.94 mmol), was added dropwise a solution of NaOH 40% ( 3 ml_). The reaction mixture was stirred 6 hours at 50 C. After this time the reaction was quenched with 1 N HCI (30 ml) and extracted with EtOAC (3 x 30 ml_). The organic phase was dried over Na2SO4 and evaporated. The crude organic product was purified by flash column chromatography (10% EtOAc in hexanes) to give the product (3.1 g, 86%) as a clear oil. 1H NMR (400 MHz, CDCI3) 6 1.4-1.44 (m, 2H), 1.76-1.80 (m, 2H), 7.44 (d, J=8.3 Hz, 1 H), 7.69 (dd,J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With tetrabutylammomium bromide; In dichloromethane; water; at 20.0℃; for 4.0h; | A mixture of 4-methyl-3-trifluorobromobenzene (33.26 g, 104.261 mmol) from step 1 above , KCN (20.43 g, 313.67 mmol) and tetrabutylammonium bromide (3.37 g, 10.45 mmol) in CH2CI2/H2O 1:1 (300 mL) was stirred at room temperature for 4 hours. The layers were separated and the organic layer washed with H2O (100 ml_) 1N HCI (100 ml_), brine, dried over Na2SO4 and then concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes) to give the product as a clear oil (14.9 g, 54%). 1H NMR (400 MHz, CDCI3) 6 3.91 (s, 2H), 7.57 (d, J=8.3 Hz, 1 H), 7.75 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.5% | With hydrogenchloride; acetic acid; at 100.0℃; for 2.0h;Inert atmosphere; | Add hydrochloric acid (2 mL, 12M) to a solution of 2-[ 4-bromo-2(trifluoromethyl)phenyl]acetonitrile (600 mg, 2.25 mmol) in acetic acid (2 mL), the mixture is stirred at 100 C for 2 h under nitrogen. The reaction mixture is concentrated to afford title 5 compound (600 mg, 89.5%) as colorless oil. 1H NMR (400MHz, CD3Cl) () = 7.82 (d, J = 1.6 Hz, 1H), 7.67 (dd, J = 1.6, 8.4 Hz, 1H), 7.29 (s, 1H), 3.83 (s, 2H). |
With sulfuric acid; acetic acid; In water; at 110.0℃;Inert atmosphere; | A mixture of <strong>[877131-92-5]2-(4-bromo-2-(trifluoromethyl)phenyl)acetonitrile</strong> (2.385 g, 9.03 mmol), water (8.5 mL), 95%sulfuric acid (9.5 mL) and acetic acid (6.5 mL) is heated to 110C, under nitrogen, overnight. The RM isallowed to cool to RT and is poured onto ice/water. The mixture is extracted three times with DCM and the combined organic layers are washed with brine, dried over anh. MgSO4, filtered and concentrated under reduced pressure affording crude 2-(4-bromo-2-(trifluoromethyl)phenyl)acetic acid as a light yellow solid (2.694 g, quantitative). LC-MS B: tR = 0.85 mm; no ionization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In water; acetonitrile; at 80.0℃;Inert atmosphere; | A solution of 4-bromo-1-(chloromethyl)-2-(trifluoromethyl)benzene (2.707 g, 9.81 mmol) in MeCN (32 mL) and water (4 mL) is treated with sodium cyanide (0.651 g, 12.80 mmol) and the mixture is heated to 80C, under nitrogen, overnight. The RM is allowed to cool to RT and is diluted with water. Acetonitrile is removedunder reduced pressure and the mixture is extracted twice with DCM. The combined organic layers are dried over anh. MgSO4, filtered and concentrated under reduced pressure. Purification by FC (from heptane to heptane/EtOAc = 7/3) affords 2-(4-bromo-2-(trifluoromethyl)phenyl)acetonitrile as a light yellow solid (2.385 g, 92%). LC-MS B: tR = 0.95 mm; no ionization. |
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