Structure of 2106-50-5
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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. : | 2106-50-5 |
Formula : | C6H3ClFNO2 |
M.W : | 175.55 |
SMILES Code : | C1=C(C(=CC(=C1)F)Cl)[N+]([O-])=O |
MDL No. : | MFCD03412200 |
InChI Key : | KQOOFMWRLDRDAX-UHFFFAOYSA-N |
Pubchem ID : | 75017 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 40.23 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.42 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.81 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.89 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.87 |
Solubility | 0.239 mg/ml ; 0.00136 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.15 |
Solubility | 0.125 mg/ml ; 0.000709 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.67 |
Solubility | 0.375 mg/ml ; 0.00214 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 |
-5.57 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) |
1.81 |
* 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 |
---|---|---|
16.7% | With sulfuric acid; nitric acid; In hexane; benzene; | (a) 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) ae added. The extract is washed with water (1+300 ml.), sodium carbonate solution (1*300 ml.), and water (1*300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C. |
16.7% | With sulfuric acid; nitric acid; In hexane; benzene; | a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1*300 ml.), are added. The extract is washed with water (1*300 ml.), sodium carbonate solution (1*300 ml.), and water (1*300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C. |
16.7% | With sulfuric acid; nitric acid; In hexane; benzene; | (a) 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1*300 ml.), sodium carbonate solution (1*300 ml.), and water (1*300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C. |
16.7% | With sulfuric acid; nitric acid; In hexane; benzene; | a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1 * 300 ml.), sodium carbonate solution (1 * 300 ml.), and water (1 * 300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C. |
16.7% | With sulfuric acid; nitric acid; In hexane; benzene; | a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1 * 300 ml.), are added. The extract is washed with water (1 * 300 ml.), sodium carbonate solution (1 * 300 ml.), and water (1 * 300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitro-fluorobenzene (51 g. 16.7%) m.p. 36-38 C. |
16.7% | With sulfuric acid; nitric acid; In hexane; benzene; | a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1 * 300 ml.), sodium carbonate solution (1 * 300 ml.), and water (1 * 300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C. |
With sodium nitrate; methanesulfonic acid; at 20 - 30℃; | A 500 mL flask was charged with commercially available 1-chloro-3-fluorobenzene (20.0 g, 0.153 mol) and methane sulfonic acid (100 mL). The reaction was vigorously stirred and sodium nitrate (13.0 g, 0.153 mol) was added in small portions to the reaction mixture while the temperature was maintained below 30 C. using a water bath for external cooling. After addition of sodium nitrate the reaction was stirred at RT for 4 hours. The reaction mixture was poured into 500 mL ice-water and the aqueous layer was extracted with dichloromethane (3×250 mL). The organic extracts were washed once with saturated NaHCO3/H2O (500 mL). The combined extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was distilled (bp 71 C., 2.3 torr) to obtain 2-chloro-4-fluoronitrobenzene as a clear oil (14.6 g, 54%, purity (GC)=84%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With sodium hydroxide;triphenylphosphine; palladium dichloride; In 1,4-dioxane; water; at 85℃; for 6h; | Example 3: Reaction of di(3,4-dichlorophenyl)borinic acid and 2-chloro-4-fluoro-1 - nitro-benzen; A reaction flask is initially charged with 0.55 g of sodium hydroxide (13.7 mM) and 50 mL of water at 15-200C.To this are metered 2,5 g of di(3,4-dichlorophenyl)borinic acid (7.8 mM) and 0.199 g of triphenylphosphine (0.76 mM) in 50 mL of dioxane. After full addition, the reaction solution is stirred at 18-22C for 40 minutes. After deoxygenation, 27 mg of palladium(ll) chloride (0.15 mM) and 1 ,3 g of 2-chloro-4-fluoro-1 -nitro-benzene (7.4 mM) are added to the reaction solution. The reaction solution is heated to 85C for 6 hours.The reaction mixture is cooled down, acidified with 2 M hydrochloric acid and the dioxane evaporated. The residue is extracted with dichloromethane and after evaporation of solvent the 3',4'-dichloro-5-fluoro-2-nitro-biphenyl is isolated by column chromatography (0.76 g, yield 36%). GC-MS: m/z = 285.9 [m-H]- |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 110℃; for 48h; | To a solution of L-proline tert-butyl ester (1.06 g, 7.5 mmol) in dry DMSO (10 ml) were added <strong>[2106-50-5]3-chloro-4-nitrofluorobenzene</strong> (1.48 g, 8.4 mmol) and diisopropylethylamine (2.60 mL, 15 mmol). The resulting solution was heated at 110 C. in a sealed tube for 48 hours. The reaction mixture was cooled to room temperature and partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water, dried over sodium sulfate, and concentrated in vacuo. Purification of the crude residue on silica gel (7:3/EtOAc-hexanes) provided 1.98 g (90%) of a pale yellow solid. 1H NMR (CD3OD) delta 8.13 (1H, d, J=2.7 Hz), 8.02 (1H, dd, J=9.3 Hz, 2.7 Hz), 6.92 (1H, d, J=9.3 Hz), 5.01 (1H, dd, J=9.2 Hz, 3.9 Hz), 3.35 (1H, m), 3.30 (1H, m), 2.31 (1H, m), 2.07 (1H, m), 2.02 (2H, m), 1.38 (9H, s). |
1.98 g (90%) | In dimethyl sulfoxide; | A. (S)-1-(3-Chloro-4-nitrophenyl)-2-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester STR330 To a solution of L-proline tert-butyl ester STR331 (1.06 g, 7.5 mmol) in dry DMSO (10 ml) were added <strong>[2106-50-5]3-chloro-4-nitrofluorobenzene</strong> (1.48 g, 8.4 mmol) and duisopropylethylamine (2.60 mL, 15 mmol). The resulting solution was heated at 110 C. in a sealed tube for 48 hours. The reaction mixture was cooled to room temperature and partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water, dried over sodium sulfate, and concentrated in vacuo. Purification of the crude residue on silica gel (7:3/EtOAc-hexanes) provided 1.98 g (90%) of a pale yellow solid. 1 H NMR (CD3 OD): d 8.13 (1H, d, J=2.7 Hz), 8.02 (1H, dd, J=9.3 Hz, 2.7 Hz), 6.92 (1H, d, J=9.3 Hz), 5.01 (1H, dd, J=9.2 Hz, 3.9 Hz), 3.35 (1H, m), 3.30 (1H, m), 2.31 (1H, m), 2.07 (1H, m), 2.02 (2H, m), 1.38 (9H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; | EXAMPLE 15 200 Parts of <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> is heated to 160 C. and stirred and 160 parts of the potassium salt of 5-methyl salicylaldehyde is added over a 30 minute period. After an exothermic reaction the mixture is heated at 150 C. for 1 hour. The mixture is cooled, ice and water are added, and it is then extracted with ether. The ether is filtered to remove insoluble material and the resultant solution is dried over sodium sulfate. The ether solvent is then evaporated and the residual oil is recrystallized from a mixture of hexane and benzene to provide 2-(2-nitro-4-fluorophenoxy)-5-methylbenzaldehyde having the following structural formula STR27 A solution of 55 parts of this material is placed in 800 parts of ethanol and hydrogenated over Raney nickel catalyst at room temperature and atmospheric pressure. |
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