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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 1000994-95-5
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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.
4.5
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CAS No. : | 1000994-95-5 |
Formula : | C8H7BrF2 |
M.W : | 221.04 |
SMILES Code : | CC(F)(F)C1=CC=C(Br)C=C1 |
MDL No. : | MFCD11110333 |
InChI Key : | QXIBKCFAFRHORF-UHFFFAOYSA-N |
Pubchem ID : | 45158847 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H227-H301-H315-H319 |
Precautionary Statements: | P210-P280-P301+P310-P305+P351+P338 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 43.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.63 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.87 |
Solubility | 0.0296 mg/ml ; 0.000134 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.38 |
Solubility | 0.0921 mg/ml ; 0.000417 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.25 |
Solubility | 0.0124 mg/ml ; 0.0000561 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
Yes |
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 |
-5.03 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.27 |
* 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 |
---|---|---|
77% | With diethylamino-sulfur trifluoride In dichloromethane at 50℃; Inert atmosphere | Example 63A1-Bromo-4-(1,1-difluoroethyl)benzene; Under argon, 3.0 g (15.07 mmol) of 1-(4-bromophenyl)ethanone were initially charged in 30 ml of dichloromethane, and 15.9 ml (120.57 mmol) of [ethyl(trifluoro-λ4-sulphanyl)amino]ethane (DAST) were added slowly. The reaction solution was then slowly warmed to 50° C. and stirred at this temperature overnight. After the reaction had ended, the reaction solution was slowly poured into ice-water. The organic phase was then separated off, and the aqueous phase was extracted three more times with dichloromethane. The combined organic phases were dried over magnesium sulphate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1). This gave 2.56 g (11.58 mmol, 77percent of theory) of the title compound as a yellowish liquid.GC-MS (Method 1): Rt=2.84 min; m/z=220/222 (M)+. |
76% | With (bis-(2-methoxyethyl)amino)sulfur trufluoride In tetrahydrofuran; methanol for 96 h; Reflux | Example 48A 1-Bromo-4-(1,1-difluoroethyl)benzene A solution of 10.0 g (50.2 mmol) of 4-bromoacetophenone in tetrahydrofuran (20 ml) was admixed with 50.0 ml (151 mmol, 50percent in tetrahydrofuran) of bis(2-methoxyethyl)aminosulphur trifluoride (Deoxofluor) and 3 drops of methanol, and then stirred under reflux for 4 days. The reaction mixture was cautiously added dropwise to a mixture of saturated aqueous sodium hydrogencarbonate solution and ice (1:1) and then extracted with diethyl ether. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by means of column chromatography (silica gel, petroleum ether/dichloromethane 3:1). Yield: 8.46 g (76percent of theory) 1H NMR (400 MHz, DMSO-d6): δ=7.70 (d, 2H), 7.52 (d, 2H), 1.96 (t, 3H). |
76% | With methanol; (bis-(2-methoxyethyl)amino)sulfur trufluoride In tetrahydrofuran for 96 h; Reflux | Example 68A1-Bromo-4-(1,1-difluoroethyl)benzene A solution of 10.0 g (50.2 mmol) of 4-bromoacetophenone in tetrahydrofuran (20 ml) was admixed with 50.0 ml (151 mmol, 50percent in tetrahydrofuran) of bis(2-methoxyethyl)aminosulphur trifluoride (Deoxofluor) and 3 drops of methanol, and then stirred under reflux for four days. The reaction mixture was cautiously added dropwise to a mixture of saturated aqueous sodium hydrogencarbonate solution and ice (1:1) and then extracted with diethyl ether. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by means of column chromatography (silica gel, petroleum ether/dichloromethane 3:1). Yield: 8.46 g (76percent of theory)1H NMR (400 MHz, DMSO-d6): δ=7.70 (d, 2H), 7.52 (d, 2H), 1.96 (t, 3H). |
59% | at 85℃; for 15 h; | Deoxo-Fluor (registered trademark) (22.2 g) was added to 1-(4-bromophenyl)ethanone (20.0 g) and the mixturewas stirred at 85°C for 15 hours. Under icecooling, ice water and an aqueous solution of potassium carbonate wereadded to the reaction solution, followed by extraction with chloroform. The solvent was evaporated under reducedpressure and the obtained residue was purified by silica gel column chromatography (hexane) to give the title compound(13.0 g, yield 59percent) as a yellow oil.1H NMR (600 MHz, CDCl3) δ ppm 1.91 (t, J=18.2 Hz, 3H), 7.50 (d, J=8.3 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H). |
25% | With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane; toluene at 20 - 85℃; for 20 h; Ionic liquid; Sealed tube | Step A: Preparation of l-bromo-4-(l,l-difluoroethyl)benzene. [00211] To a vial equipped with a magnetic stir bar were added a solution of l-(4- bromophenyl)ethanone (295 mg, 1.48 mmol) in anhydrous DCM (3.0 mL) followed by a 50percent solution of Deoxofluor® in toluene (1.6 mL, 4.45 mmol) at room temperature under N2 and the vial was sealed. The reaction mixture was stirred for approximately 15 h at room temperature, but little conversion had taken place. The mixture was concentrated, treated with additional Deoxofluor® solution (0.66 mL, 1.79 mmol),and warmed to and stirred at 85 °C under N2 for 5 h. The reaction mixture was cooled to 0 °C and carefully quenched by adding sat'd aq NaHC03 dropwise until gas evolution ceased. The bi-phasic mixture was extracted with DCM (2 x 5 mL), and the combined extracts were dried over Na2S04, filtered, and concentrated. The residue was purified by column chromatography (Si02, 0-^50 EtOAc in hexanes) to afford the title compound (83 mg, 25percent)as a clear liquid: 1H NMR (400 MHz, CDC13) δ 7.58 - 7.53 (m, 2H), 7.41 - 7.35 (m, 2H), 1.90 (t, J = 18.1 Hz, 3H); 19F NMR (376 MHz, CDC13) δ -87.86; IR (Thin Film) 1599, 1294, 1089 cm"1; EIMS mlz 220/221. |
17.26 g | With (bis-(2-methoxyethyl)amino)sulfur trufluoride In chloroform at 50℃; for 35 h; Inert atmosphere | Under argon atmosphere, into a 500-ml reaction vessel made of tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA) and equipped with a stirring apparatus were placed 25 g (126 mmol) of 4-bromoacetophenone, 111 g (500 mmol) of bis(2-methoxyethyl)aminosulfur trifluoride, and 250 ml of anhydrous chloroform, so that a homogeneous solution was prepared. And then, the solution was reacted at an internal temperature of about 50°C for 35 hours. Subsequently, the reaction solution was cooled to room temperature, and then the reaction solution was added to 1000 ml of a saturated aqueous solution of sodium hydrogen carbonate, which was cooled in ice. Subsequently, the mixture was subjected to extraction with 500 ml of chloroform. The solvent was distilled off under a reduced pressure, and then the reaction mixture was purified by silica gel column chromatography (hexane: 100 vol percent), to provide 17.26 g of Compound (4-1) in the form of a colorless liquid. [0134] The properties of Compound (4-1) were as follows. 1H-NMR (400MHz, CDCl3, 8 (ppm)); 1.90 (3H, t, J=18.1Hz), 7.54 (2H, d, J=2.3Hz), 7.57 (2H, d, J=2.4Hz) CI-MS; 222 (M+2) |
17.26 g | With (bis-(2-methoxyethyl)amino)sulfur trufluoride In chloroform at 50℃; for 35 h; Inert atmosphere | Under argon atmosphere, into a 500-ml reaction vessel 30 made of tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA) and equipped with a stirring apparatus were placed 25 g (126 mmol) of 4-bromoacetophenone, 111 g (500 mmol) of bis(2-methoxyethyl)aminosulthr trifluoride, and 250 ml of anhydrous chloroform, so that a homogeneous solution was prepared. And then, the solution was reacted at an internal temperature of about 50° C. for 35 hours. Subsequently, the reaction solution was cooled to room temperature, and then the reaction solution was added to 1000 ml of a saturated aqueous solution of sodium hydrogen carbonate, which was cooled in ice. Subsequently, the mixture was subjected to extraction with 500 ml of chloroform. The solvent was distilled off under a reduced pressure, and then the reaction mixture was purified by silica gel column chromatography (hexane: 100 vol percent), to provide 17.26 g of Compound (4-1) in the form of a colorless liquid.The properties of Compound (4-1) were as follows. ‘H-NMR (400 MHz, CDC13, ö (ppm)); 1.90 (3H, t, J=18. 1 Hz), 7.54 (2H, d, J=2.3 Hz), 7.57 (2H, d, J=2.4 Hz)CI-MS; 222 (M+2)4045 |
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