Structure of 655235-61-3
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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. : | 655235-61-3 |
Formula : | C10H4BrClF3N |
M.W : | 310.50 |
SMILES Code : | FC(C1=NC2=C(Br)C=CC=C2C(Cl)=C1)(F)F |
MDL No. : | MFCD00174293 |
InChI Key : | KKGSBQKOZKBRKL-UHFFFAOYSA-N |
Pubchem ID : | 628370 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.1 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 59.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.51 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.06 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.31 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.95 |
Solubility | 0.00346 mg/ml ; 0.0000112 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.42 |
Solubility | 0.0118 mg/ml ; 0.0000381 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.04 |
Solubility | 0.000284 mg/ml ; 0.000000914 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) |
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 |
-5.05 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 |
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) |
1.7 |
* 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 |
---|---|---|
72% | With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In ethanol; for 3.0h;Heating / reflux; | A suspension of 2.00 g (6.25 mmol) 8-bromo-4-chloro-2-trifluoromethylquinoline (commercially available from Maybridge, Cornwall, UK), 258 mg (0.31 mmol) PdCl2dppf CH2Cl2, 1.29 g (9.37 mmol) potassium vinyl tetrafluoroborate and 0.88 ml (6.28 mmol) triethylamine in 40 ml ethanol was heated at reflux for 3 h. The resulting yellow suspension was filtered and the filtrate evaporated to dryness. The residue was suspended in ethyl acetate, filtered and the filtrate extracted with water. The organic layer was evaporated to dryness and the isolated crude product purified by silica gel chromatography (hexane) to yield 1.17 g (72%) of the title compound as white crystals. MS: 257.1 (M+). 1H-NMR (300 MHz, CDCl3): 5.58 (dd, J=I Ll, LlHz, IH); 6.07 (dd, J=17.8, LlHz, IH); 7.75 (t, J=7.7Hz, IH); 7.81 (s, IH); 7.99 (dd, J=17.8, I LlHz, IH); 8.09 (d, J=7.2Hz, IH); 8.23 (d, J=8.4Hz, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 125.0℃; for 12.0h; | To a solution of <strong>[655235-61-3]8-bromo-4-chloro-2-(trifluoromethyl)quinoline</strong> (60 mg, 193.24 umol, 1 eq) in DMSO (1 mL) were added N- [(1R,3S)-3-aminocyclohexyl]-4-methoxy-benzamide (52.78 mg, 212.56 umol, 1.1 eq) and DIEA (49.95 mg, 386.48 umol, 67.32 uL, 2 eq) . The mixture was stirred at 125 C for 12 hr. The reaction mixture was added water (20 mL) and extracted with EA (20 mL×2). The organic layer was washed with brine, dried by Na2SO4. The solution was concentrated to give the residue. The residue was purified by prep-TLC (SiO2, PE: EA = 2:1) to afford N-[(1R,3S)-3-[[8-bromo-2-(trifluoromethyl)-4-quinolyl]amino]cyclohexyl]-4-methoxy- benzamide (60 mg, 114.86 umol, 59% yield). LCMS-ESI (m/z) calculated: 522.6; found 522.1/524.1 [M+H]+, RT = 0.977 min (Method 2). |
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