Structure of 2,5-Difluoronitrobenzene
CAS No.: 364-74-9
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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. : | 364-74-9 |
Formula : | C6H3F2NO2 |
M.W : | 159.09 |
SMILES Code : | C1=C(F)C=CC(=C1[N+](=O)[O-])F |
MDL No. : | MFCD00007054 |
InChI Key : | XNJAYQHWXYJBBD-UHFFFAOYSA-N |
Pubchem ID : | 67767 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 35.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.46 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.71 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.73 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.66 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.34 |
Solubility | 0.734 mg/ml ; 0.00462 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.44 |
Solubility | 0.573 mg/ml ; 0.0036 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.33 |
Solubility | 0.753 mg/ml ; 0.00473 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) |
No |
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 |
-5.95 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 |
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) |
1.78 |
* 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 |
---|---|---|
1-[5-Fluoro-2-(1-methyl-piperidin-3-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea Steps 1-2: According to procedure for compound 300, using 1,4-difluoro-2-nitrobenzene and 1-methyl-3-hydroxymethyl piperidine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(ii) 2-Mercapto-5-fluorobenzthiazole yellow solid mp 125 C. (dec) (from 1,4-difluoro-2-nitrobenzene) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In tetrahydrofuran; hexane; | EXAMPLE 1 Ethyl 3-(4-fluoro-2-nitroanilino)-1-methylpyrazole-4-carboxylate A solution of <strong>[21230-43-3]ethyl 3-amino-1-methylpyrazole-4-carboxylate</strong> (Helv. Chim. Acta (1959) 42 349) (17 g) in dry tetrahydrofuran (250 ml) was stirred under nitrogen at -10 C. n-Butyl lithium (75 ml of 1.84 molar solution in hexane) was added at -10 to -15 C. The mixture was stirred at -15 C. for 10 minutes and a solution of 2,5-difluoronitrobenzene (16 g) in dry tetrahydrofuran (50 ml) was added at -15 to -10 C. The solution was warmed at room temperature and stirred for 1 hour. The ink-blue solution was poured into 500 ml of a 1:1 mixture of hydrochloric acid (2 M) and ice-brine, extracted with chloroform (3*250 ml), washed with water (2*250 ml), dried with magnesium sulphate and evaporated to dryness. The brick-red residue was crystallized from ethanol (800 ml) to give the title compound having a m.p. of 162 C. The following compounds were similarly prepared using the above process. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
STARTING MATERIAL SYNTHESIS EXAMPLE 8 In the same manner as in Starting Material Synthesis Example 4 and using <strong>[7311-95-7]ethyl 2-aminobenzo[b]thiophene-3-carboxylate</strong>, 2,5-difluoronitrobenzene and dimethyl sulfoxide, ethyl 2-(4-fluoro-2-nitroanilino)benzo[b]thiophene-3-carboxylate is obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate; In N,N-dimethyl-formamide; at 140.0℃; for 0.2h;Microwave irradiation; | General procedure: A mixture of benzenesulfonamides (1, 1.0 mmol), halogenated nitrobenzene(2, 1.0 mmol) and K2CO3 (1.1 mmol) were dissolved in DMF in a microwave tube. Then, the reaction mixture was irradiated in a microwave apparatus at 140 C for 12 minutes. After the reaction mixture was cooled to ambient temperature, the product was concentrated, and the crude mixture was purified by column chromatography on silica gel to the desired products 3. |
89% | With potassium carbonate; In N,N-dimethyl-formamide; at 140.0℃; for 0.25h;Microwave irradiation; | Add 1 mmol of 4-bromo-1-naphthalenesulfonamide and 1.1 mmol of 2,5-difluoronitrobenzene to a reaction tube containing 1.5 mmol of anhydrous potassium carbonate and 5 mL of N,N-dimethylformamide (DMF). Then cover the reaction tube cover,Microwave radiation reaction at 140 degrees Celsius for 15 minutes, then cooled to room temperature.After opening, acidify, extract ethyl acetate and combine the organic phase.After drying over anhydrous sodium sulfate, the filtrate was dried under reduced pressure and column chromatography.The eluent is petroleum ether and acetone. Made a yellow solid,Yield: 89%; |
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