Structure of 1032903-50-6
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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.
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CAS No. : | 1032903-50-6 |
Formula : | C10H12ClNO3 |
M.W : | 229.66 |
SMILES Code : | O=[N+](C1=C(OC(C)C)C=C(Cl)C(C)=C1)[O-] |
MDL No. : | MFCD11499001 |
InChI Key : | BXIHEXKVDALKGM-UHFFFAOYSA-N |
Pubchem ID : | 45790324 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 61.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.36 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.34 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.32 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.57 |
Solubility | 0.0623 mg/ml ; 0.000271 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.34 |
Solubility | 0.0105 mg/ml ; 0.0000458 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.35 |
Solubility | 0.102 mg/ml ; 0.000445 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 |
-5.22 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) |
2.22 |
* 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 |
---|---|---|
95% | With caesium carbonate; at 60℃; for 16.0h; | 2-Chloro-4-fluoro-5-nitrobenzene (25 g, 131 mmol) was dissolved in isopropanol (250 mL) and cesium carbonate(208 g, 659 mmol) was added thereto. The reaction mixture was stirred at 60 C for 16 hours. The reaction mixture was cooled to room temperature and the reaction mixture was concentrated under reduced pressure. The residue wasdissolved in ethyl acetate (250 mL) and then water (250 mL) was added. The separated organic phase was dried overanhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purifiedby silica gel column chromatography (petroleum ether: ethyl acetate = 19: 1) to deliver a yellow solid 13-d (28.7 g, yield:95%).1H-NMR (400MHz, DMSO-d6) delta: 7.90 (d, J=0.6Hz, 1H), 7.52 (s, 2H), 7. 86 (m, 1H), 2.30 (s, 3H), 1.27 (d, J=6Hz, 6H) ppm. |
86.3% | With potassium hydroxide; at 20℃; | 1.5 L of isopropanol, <strong>[112108-73-3]1-chloro-5-fluoro-2-methyl-4-nitrobenzene</strong> (260 g)Potassium hydroxide (116g) was added to complete the reaction at a temperature of 20 C to monitor the disappearance of the raw materials. The stirring was stopped and the reaction solution was added to 5L of water overThe product was filtered and the filter cake was dried to give 1-chloro-5-isopropyloxy-2-methyl-4-nitrobenzene, 271 g, yield: 86.3%. |
82% | With caesium carbonate; at 60℃; | The title compound <strong>[112108-73-3]2-chloro-4-fluoro-5-nitrotoluene</strong> (i.e., compound 2-1, 14.2 g, 74.9 mmol) was dissolved in isopropanol (100.0 mL)Cesium carbonate (122.0 g, 374.4 mmol) was added,The reaction was carried out at 60 C overnight.After completion of the reaction, the mixture was concentrated to remove isopropanol,Poured into 500.0mL water, extracted with ethyl acetate, the organic phase was dried with anhydrous sodium sulfate, concentrated,Compound No. 2-2 (14.4 g) was obtained in a yield of 82.0%. |
82% | With caesium carbonate; at 60℃; | The title compound <strong>[112108-73-3]2-chloro-4-fluoro-5-nitrotoluene</strong> (i.e., Compound 2-1, 14.2 g, 74.9 mmol) was dissolved in isopropanol (100.0 mL), cesium carbonate (122.0 g, 374.4 mmol) The reaction mixture was concentrated at 60 C overnight. After completion of the reaction, the mixture was concentrated to remove isopropanol, poured into 500.0 mL of water, extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated to give Compound 2-2 (14.3 g), yield: 82.0%. |
74.4% | With caesium carbonate; at 60℃; for 24.0h; | 1-Chloro-5-fluoro-2-methyl-4-nitrobenzene (3.260 g, 17.197 mmol)Cesium carbonate (28.015 g, 85.984 mmol) was added to a solution ofPropanol (35 mL) at 60 C was stirred at the same temperature for 24 hours, and then the temperature was lowered to room temperature to terminate the reaction. The reaction mixture was filtered through a paper filter to remove the solid. The solvent was removed from the filtrate under reduced pressure, water was poured into the resulting concentrate, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution,The water was removed with magnesium sulfate, filtered and concentrated under reduced pressure.The concentrate was purified by column chromatography (SiO2, 40 g cartridge; ethyl acetate / hexane = 5%) and concentrated to obtain 2.938 g (74.4%) of 1-chloro-5-isopropoxy-2-methyl-4-nitrobenzene As a light brown solid. |
With caesium carbonate; at 60℃; | To a solution of 25 g (0.131 mol) of <strong>[112108-73-3]2-chloro-4-fluoro-5-nitrotoluene</strong> in 250 ml of 2- propanol is added 208 g (0.659 mol, 5 eq.) of Cs2CO3. The mixture is stirred at 6O0C overnight and most of the 2-propanol is evaporated under reduced pressure. Water is added and the solution is extracted with EtOAc. The organic layers are combined, dried over MgSO4, concentrated and the crude product filtrated over a silica plug (eluent: 95/5 hexanes/EtOAc) to afford 2-chloro-4-/,sopropoxy-5-nitrotoluene as a pale yellow fluffy solid. | |
With potassium carbonate; for 40.0h;Reflux; | 2-chloro-4-fluoro-5-nitro-toluene was dissolved in 1200 ml of isopropanol and 2 L of a three-necked flask was added. Add 429 g of anhydrous potassium carbonate powder. Stir under the temperature to reflux. The reaction was kept under reflux for ~ 40 hours. Concentrate to remove most of the isopropanol. Add 2L of water, And extracted twice with ethyl acetate. The ethyl acetate layer was combined, Washed. Concentrated ethyl acetate, To give a brown 2-chloro-4-isopropoxy _5_ nitro - toluene. | |
With potassium carbonate; for 40.0h;Reflux; | EXAMPLE 2 Preparation of 2-chloro-4-isopropyoxy-5-nitrotoluene <strong>[112108-73-3]2-chloro-4-fluoro-5-nitrotoluene</strong> was dissolved in 1200 ml of isopropanol and the solution was added in a 2 L of a three-necked flask. 429 g of anhydrous potassium carbonate powder was added therein. The mixture was heated to reflux under stirring. The reaction was conducted for about 40 hours under reflux. Most of the isopropanol was removed via concentration. 2 L of water was added and the mixture was extracted with ethyl acetate twice. The ethyl acetate layer was combined and washed with water. Ethyl acetate layer was concentrated to give 2-chloro-4-isopropoxy-5-nitrotoluene as a brown substance. H NMR Data 1H NMR (CDCl3): delta7.71(s, 1H), 7.07(s, 1H), 4.61(m, 1H), 2.34(s, 3H), 1.40(d, 3.2, 6H). |
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