Structure of 179552-73-9
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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. : | 179552-73-9 |
Formula : | C14H7Cl2FN4O2 |
M.W : | 353.14 |
SMILES Code : | O=[N+](C1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1Cl)[O-] |
MDL No. : | MFCD19440823 |
InChI Key : | ALJPGKSDBZFNBR-UHFFFAOYSA-N |
Pubchem ID : | 21847817 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 23 |
Num. arom. heavy atoms | 16 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 87.88 |
TPSA ? Topological Polar Surface Area: Calculated from |
83.63 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.15 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.06 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.24 |
Solubility | 0.00201 mg/ml ; 0.0000057 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.08 |
Solubility | 0.000293 mg/ml ; 0.00000083 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.75 |
Solubility | 0.0000632 mg/ml ; 0.000000179 mol/l |
Class? Solubility class: Log S scale |
Poorly 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 |
No |
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) |
Yes |
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 |
-5.19 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.52 |
* 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 |
---|---|---|
67% | 1) A mixture (about 3:1, 52.0 g; described in Leonard et al., J. Org. Chem. 1975, 40, 356-363) of 7-chloro-6-nitro-3H-quinazolin-4-one and 7-chloro-8-nitro-3H-quinazolin-4-one and DMF (0.7 mL) were added to thionyl chloride (200 mL) and the mixture was heated under reflux for 4 hrs. The reaction mixture was concentrated to dryness and toluene (150 mL) was added. The mixture was concentrated further. This step was repeated twice and dichloromethane (280 mL) was added to the residue. The mixture was stirred at room temperature. To this suspension was added dropwise a solution (760 mL) of 3-chloro-4-fluoroaniline (36.9 g, 253.6 mmol) in isopropanol. Dichloromethane (300 mL) was added and the mixture was stirred, at 20 C. for 20 min. Hexane (600 mL) was added under ice-cooling, and stirring was continued at 20 C. The precipitate was collected by filtration, washed with hexane (200 mL×2) and dried under reduced pressure. The obtained solid was added to methanol (1 L)-water (120 mL), and triethylamine (30 mL) was added with stirring under ice-cooling. After stirring at room temperature for 1 hr, the precipitate was collected by filtration and washed with water (700 mL×2). The crudely purified substance (65 g) was suspension-washed with acetonitrile (1.2 L) with heating, and collected by filtration to give the objective (7-chloro-6-nitro-4-quinazolinyl)-(3-chloro-4-fluorophenyl)amine (54.6 g, 67%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | To a 250 mL four-necked flask was added 2.3 g (10.2 mmol)7-chloro-6-nitroquinazolin-4-one (7), 3 to 4 drops of DMF and 10 mL of thionyl chloride,Stirring to reflux, 30min after the solid completely dissolved, reflux reaction 2.5h,Sulfur disulfide was evaporated to give a pale yellow solid.To the reaction flask was added 1.8 g (12.2 mmol)3-chloro-4-fluoroaniline and 1,4-dioxane solution 25mL,Added, the reaction was yellow turbid liquid, slowly warming to 90 ,And reacted at that temperature for 1 h. After cooling to room temperature, pour into the water,Precipitation of light orange solid, with saturated aqueous sodium bicarbonate solution to neutral,Filtered, washed with water and dried to give 3.5 g of an orange solid, 98% yield,Purity 96%. | |
70% | The phosphorus oxychloride (phosphorous oxy chloride) 10 ml melting was dissolved in 7- chloro- 6- nitro quinazoline - 4 (3H) -one 11 (5 g, 22.16 mmol) which were the starting material in the CH 3 CN of 30 ml was added and the mixture was stirred at 80 for 5 hours. After 5 hours, 3-chloro-4-fluoroaniline (3.871 g, 26.59 mmol) dissolved in 10 ml of dioxane was added dropwise thereto, followed by stirring for 1 hour. After the completion of the reaction was confirmed by TLC, the pH of the solution was adjusted to between 8 and 10 with 2N KOH solution, and the resulting solid was filtered. The solid compound was washed with water and ethanol, and then Compound 12 (6.574 g, 18.61 mmol , 70%) was obtained |
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