Structure of 162364-72-9
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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. : | 162364-72-9 |
Formula : | C16H13ClN2O2 |
M.W : | 300.74 |
SMILES Code : | C(C1=CC=CC=C1)OC2=C(C=C3C(=C2)N=CN=C3Cl)OC |
MDL No. : | MFCD04115120 |
InChI Key : | LBGIYCBNJBHZSZ-UHFFFAOYSA-N |
Pubchem ID : | 10661998 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 16 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 82.02 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.1 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.94 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.59 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.47 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.49 |
Solubility | 0.00981 mg/ml ; 0.0000326 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.57 |
Solubility | 0.00812 mg/ml ; 0.000027 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.72 |
Solubility | 0.0000569 mg/ml ; 0.000000189 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 |
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) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.34 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 |
0.0 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 |
---|---|---|
81% | In isopropyl alcohol; | The starting material was prepared as follows: A mixture of <strong>[84478-72-8]4-chloro-2-fluoro-5-hydroxyaniline</strong> (2.5 g, 15 mmol), (as described in EP 61741 A2), and 7-benzyloxy-4-chloro-6-methoxyquinazoline (4.2 g, 14 mmol), (prepared as described for the starting material in Example 4 but with an aqueous work up), in isopropanol was heated at reflux for 2 hours. The mixture was then allowed to cool and the solid product collected by filtration, washed with isopropanol and dried to give 7-benzyloxy-4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxyquinazoline hydrochloride (4.8 g, 81%). 1H NMR Spectrum: (DMSOd6) 3.98(s, 3H); 5.18(s, 2H); 7.05(d, 1H); 7.18-7.27(m, 7H); 8.06(s, 1H); 8.38(s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Preparation of l-(3-H"7-(benzyloxy)-6-methoxyquinazolin-4-ylloxyl-2-fluoro-6- nitrophenvDacetone l-(2-Fluoro-3-hydroxy-6-nitrophenyl)-propan-2-one (4.286 g) was suspended in acetonitrile(16 ml) and cooled to -5C. To the slurry was added aqueous sodium hydroxide (0.93 ml of io 46.9%w/w solution). A line wash of acetonitrile (16 ml) was applied.This cold solution was added to a solution of 7-(benzyloxy)-4-chloro-6-methoxyquinazoline (4.26 g) in anisole (28.8 ml) at 80C over 15 minutes. A line wash of acetonitrile (16 ml) was applied. The mixture was heated at 8O0C for 21 hours. The stirrer was stopped and the lower aqueous layer separated. The upper organic layer was washed further with water (6 ml) at is 8O0C.The batch was cooled to 200C and concentrated under reduced pressure (130 mbar), allowing the batch temperature to reach 1000C, collecting 24 ml of distillate. The batch temperature was adjusted to 65C and a solution of water (4 ml) in methanol (28 ml) added. The mixture was cooled to 200C and the product filtered. The filter cake was washed with methanol (2 x20 12 ml) and dried in a vacuum oven at overnight to give l-(3-[7-(benzyloxy)-6- methoxyquinazolin-4-yl]oxy}-2-fluoro-6-nitrophenyl)acetone (4.543 g, 67% of theory). IH NMR Spectrum (400 MHz, DMSO-J6) delta ppm 2.29 (s, 3 H) 4.00 (s, 3 H) 4.27 (s, 2 H) 5.37 (s, 2 H) 7.38 (m, 1 H) 7.44 (m, 2 H) 7.53 (m, 2 H) 7.56 (s, 1 H) 7.62 (s, 1 H) 7.77 (dd, J=9.1, 7.8 Hz, IH) 8.12 (dd, J=9.05, 0.81 Hz, 1 H) 8.59 (s, 1 H)25 Mass Spectrum [M+H]+ |
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