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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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Structure of 123572-65-6
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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. : | 123572-65-6 |
Formula : | C7H3F4NO3 |
M.W : | 225.10 |
SMILES Code : | FC(F)(F)OC1=CC(F)=CC=C1[N+]([O-])=O |
MDL No. : | MFCD15527446 |
Boiling Point : | No data available |
InChI Key : | VBATUITURYFZIU-UHFFFAOYSA-N |
Pubchem ID : | 14473250 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H311-H331 |
Precautionary Statements: | P261-P264-P270-P271-P280-P285-P302+P352-P304+P340-P310-P330-P361-P403+P233-P405-P501 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 7.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.65 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.9 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.31 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.23 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.16 |
Solubility | 0.156 mg/ml ; 0.000691 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.72 |
Solubility | 0.0432 mg/ml ; 0.000192 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.69 |
Solubility | 0.457 mg/ml ; 0.00203 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) |
Yes |
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 |
-5.61 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 |
0.0 |
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 |
2.0 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) |
2.14 |
* 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 |
---|---|---|
42% | With sulfuric acid; potassium nitrate; at 0 - 5℃; for 2h;Inert atmosphere; | <strong>[1077-01-6]1-fluoro-3-(trifluoromethoxy)benzene</strong> (7.5 g, 41.6 mmol) was dissolved in concentrated sulfuric acid (30 mL),and the mixuture was cooled to 0 C. KNO3 (1.04 g, 10.25 mmol) was added slowly in batches. The internal temperatureis keeped below 5 C. Upon completion of the addition, the mixture was stirred for 2 hours. An eice-water mixture (about50 mL) was added. The reaction solution was extracted with methyl tert-butyl ether (2033 mL), and the organic phaseswere combined, dried and filtered. The filtrate was concentrated and purified by flash silica gel column chromatographyto obtain 4-fluoro-1-nitro-2-(trifluoromethoxy)benzene (4.0 g, 42%). |
16% | With sulfuric acid; nitric acid; at -10℃; | (Comparative Example 6); 4-Fluoro-l-nitro-2- (trifluoromethoxy) benzeneFuming nitric acid (20 mL) was added dropwise to concentrated sulfuric acid (40 ml) under cooling (-100C), and subsequently, 1- fluoro-3- (trifluoromethoxy) benzene (15 g, 83 mmol) was added to the mixture at -100C, and the mixture was stirred for 0.5 hours. After the mixture was added into ice-water to stop the reaction, it was extracted with dichloromethane . After the obtained organic layer was washed with a IN aqueous sodium hydroxide solution and water, it was dried with anhydrous sodium sulfate. After filtration, the solution was concentrated and the residue was purified by silica gel column chromatography (100:0-97:3, hexane : ethyl acetate) to give the title compound (3.1 g, 16%) as an oil.1H-NMR (400 MHz, CDCl3) delta: 8.10 (IH, dd, J = 5.5, 9.4 Hz) , 7.23-7.15 (2H, m) . |
12 g | With sulfuric acid; potassium nitrate; at 0℃; for 3h;Cooling with ice; | Under ice cooling mixture of 3-fluoro - trifluoromethoxyphenyl (20g) was dissolved in 40 ml of concentrated sulfuric acid, with rapid stirringWas added portionwise potassium nitrate (28g), was stirred at 0oC 3 hours and stirred at room temperature overnight, the reaction solution was carefullyGo on into 1 kg ice, stirred for 30 minutes, extracted with ethyl acetate, dried over sodium sulfate, filtered, and the filtrate was evaporated, the residue was purified by column chromatography to give 12 g pale yellow liquid. |
0.5 g | With sulfuric acid; nitric acid; at -10 - 20℃; for 0.5h; | To a 100 mL round-bottomed flask were added concentrated H2SO4 (25 mL), fuming HNO3 (25 mL), and <strong>[1077-01-6]1-fluoro-3-(trifluoromethoxy)benzene</strong> (9.0 g, 50 mmol) at -10 C. in sequence. The mixture was stirred at rt for 30 min then poured onto ice and extracted with EtOAc (3*20 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution (30 mL), brine (30 mL), dried over anhydrous Na2SO4, concentrated to dryness, and purified by FCC to give the title compound as a pale-yellow oil (0.50 g). 1H NMR (300 MHz, CDCl3): delta 8.21-8.14 (m, 1H), 7.21-7.12 (m, 2H). |
8.5 g | With sulfuric acid; potassium nitrate; at -5 - 0℃; for 1h; | Add 20 mL of concentrated sulfuric acid to a 250 mL three-necked flask.The ice salt bath is cooled to -5-0 C,Adding m-fluorotrifluoromethoxybenzene(10 g, 60 mmol), then potassium nitrate (5.9 g, 60 mmol) was added portionwise.The reaction was stirred at 0 C for 1 h.Slowly pour the reaction into the iceIn water, extracted with ethyl acetate (40 mL×3) three times, and the organic phases were combined.Wash 3 times with saturated saline (20mL × 3),Dry over anhydrous sodium sulfate for 0.5 h, suction filtration under reduced pressure.The filtrate was concentrated under reduced pressure at 45 C to give 8.5 g of pale yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; nitric acid; at 0 - 20℃; | 11A) 4-Fluoro-1-nitro-2-trifluoromethoxy-benzene To 1-fluoro-3-trifluoromethoxybenzene (1 mL) was added concentrated sulfuric acid (1 mL) at 0 C. To the cold solution was added dropwise (0.7 mL) of a solution made from concentrated nitric acid (1 mL) and concentrated sulfuric acid (1 mL). The reaction was slowly allowed to warm to room temperature then poured onto ice and extracted with ether. The organic layer was separated and washed with sodium hydroxide 1N, then brined and dried over magnesium sulfate. The solvent was removed under reduce pressure at room temperature. A pale yellow oil (1 g) was recovered and used without further purification. |
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