Structure of 35764-15-9
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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. : | 35764-15-9 |
Formula : | C8H3BrF3N |
M.W : | 250.02 |
SMILES Code : | C1=C(C(=CC=C1C(F)(F)F)C#N)Br |
MDL No. : | MFCD06659467 |
InChI Key : | YQDJZASWOJHHGY-UHFFFAOYSA-N |
Pubchem ID : | 3015802 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.86 |
TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.08 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.49 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.69 |
Solubility | 0.0506 mg/ml ; 0.000202 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.39 |
Solubility | 0.101 mg/ml ; 0.000405 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.23 |
Solubility | 0.0148 mg/ml ; 0.0000593 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 |
-5.54 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) |
1.93 |
* 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 tetra-(n-butyl)ammonium iodide; caesium carbonate;POPd; In water; N,N-dimethyl-formamide; at 150.0℃; for 0.166667h;Microwave irradiation; | Into a 5 mL microwave vial were charged methyl 3-(5-methylpyridin-2-yl)-5-(4,4,5,5- tetramethyl-l ,3,2-dioxaborolan-2-yl)benzoate (300 mg, 0.85 mmol), 2-bromo-4- (trifluoromethyl)benzonitrile (425 mg, 1.70 mmol), cesium carbonate (1.38 g, 4.25 mmol), tetra-n- butylammonium iodide (314 mg, 0.85 mmol), POPd (43 mg, 0.085 mmol), water (0.6 mL) and NN- dimethylformamide (3 mL). The reaction mixture was subjected to microwave irradiation at 150 0C for 10 mins. After cooling, the reaction mixture was extracted with ethylacetate. The organic layer was washed with brine, dried, and concentrated under reduced pressure to afford the residue which was purified by silica gel column to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In ethanol; water; toluene; for 24.0h;Reflux; | 2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline is dissolved in toluene and placed in a two-neck flask.Add Tripotassium phosphate, Pd (PPh3) 2Cl2 and Ethanol dissolved in water. After 5 minutes, add 2-bromo-4- (trifluoromethyl) benzonitrile. Allow to reflux for 24 hours. When the reaction is complete, extract with CH2Cl2. Purification by silica gel column (yield: 73%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.8% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; toluene; at 6.0℃; for 110.0h; | To a solution of (3-(methoxycarbonyl)phenyl)boronic acid (324 mg, 1.8 mmol, Eq: 1.5) in toluene (5 mL) and water (500 muEpsilon) was added <strong>[35764-15-9]2-bromo-4-(trifluoromethyl)benzonitrile</strong> (300 mg, 1.2 mmol, Eq: 1) and SPhos (49.3 mg, 120 muiotaetaomicron, Eq: 0.1) and potassium phosphate tribasic anhydrous (764 mg, 3.6 mmol, Eq: 3) and palladium(II) acetate (13.5 mg, 60 muiotaetaomicron, Eq: 0.05). The reaction mixture was stirred for 6 hours at 110C.The reaction mixture was poured on 30 mL 10% aqueous NaHC03 solution and 30 mL EtOAc and the layers were separated. The aqueous layer was extracted a second time with 30 mL EtOAc. The organic layers were washed with 30 mL brine, dried over MgS04, filtered and concentrated under vacuum.The residue was purified by silica gel chromatography to yield methyl 3-[2-cyano-5-(trifluoromethyl)phenyl]benzoate (338 mg, 73.8%). GCMS (EI): m/z = 305.1 [M+H]+. |
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