Structure of 98349-25-8
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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. : | 98349-25-8 |
Formula : | C15H13F2NO3 |
M.W : | 293.27 |
SMILES Code : | O=C(C1=CN(C2CC2)C3=C(C=C(F)C(F)=C3)C1=O)OCC |
MDL No. : | MFCD01646378 |
InChI Key : | QYGNYHKBMNUIJN-UHFFFAOYSA-N |
Pubchem ID : | 9817544 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 21 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 72.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.95 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.97 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.58 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.93 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.99 |
Solubility | 0.302 mg/ml ; 0.00103 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.61 |
Solubility | 0.72 mg/ml ; 0.00246 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.41 |
Solubility | 0.0113 mg/ml ; 0.0000385 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-6.69 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.37 |
* 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 |
---|---|---|
With sulfuric acid; sodium acetate; acetic acid; In water; | Example 2 1500 g of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, 128.4 g of water, and 4500 g of acetic acid were introduced and 53 g of sulfuric acid were added. The mixture was heated at reflux for 4 hours. 2020 ml of distillate were then distilled off until a bottom temperature of 109 C. was reached. The suspension was then cooled to 80 C. and 2204 g of 4% strength by weight sodium acetate solution were added dropwise. The pH was then in the range 3 to 4. The mixture was then cooled to 20 C. and the solid was filtered off with suction. The. solid was washed with 2000 ml of water and dried in vacuo at 50 C. 1329 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid were isolated, which corresponds to a yield of 98%. | |
In hydrogenchloride; | 1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid A suspension of 4.1 g (13.3 mmol) of ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate in 150 ml of 6N hydrochloric acid was refluxed for six hours, then cooled to room temperature. The solids were filtered, washed with water and ether, and dried to give 3.2 g of the title compound, mp >300 C. The following compounds were prepared in a similar fashion: | |
With sulfuric acid; In water; acetic acid; | EXAMPLE 10 1-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid A solution of 6,8 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, ethyl ester in a mixture of 46 ml of glacial acetic acid, 35 ml of water and 4.5 ml of concentrated sulfuric acid was refluxed for 1.5 hours. The resulting suspension was cooled in an ice bath, the solid collected, washed with cold water, dried and recrystallized from hot dimethylformamide, giving 5 g of the desired compound, mp 288-290 C. |
With hydrogenchloride; water; acetic acid; for 2.5h;Reflux; | Crude compound 1.3 (700 mg, 2.39 mmol, 1 eq) was refluxed with concentrated HC1 mL) and concentrated AcOH (13 mL) for 2.5 hours. The mixture was allowed tocool to room temperature, and the resulting precipitate was filtered, washed with water ( mL) and dried to give the crude product 1.4 mg, 90.4 % yield) as a white solid which was used in the successive reaction without further purification. 1H NMR (400 MHz, TFA-cl) 6 9.34 (ci, J = 3.53 Hz, 1H), 8.32 - 8.40 (m, 2H), 3.99 - 4.06 (m, 1H), 1.54 - 1.62 (m, 2H), 1.35 (br. 5., 2H); JR (umax/cm1) 1719, 1614, 1556, 1421, 1332, 1303, 1289, 1231, 1204, 1056, 1033, 1020, 891, 806, 778, 748, 719, 606; LC-MSRetention time 3.37 minutes, found 265.9 [M+H] calculated for C13H9F2N03266.22[M+H]. | |
In sulfuric acid; | A suspension of 7.85 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, ethyl ester in 220 ml of 2N sulfuric acid was heated at 100 C. overnight, then cooled in an ice bath. The solid was collected, washed with water and dried, giving 6.81 g of the desired compound, mp 292-293 C. |
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