Structure of 71082-51-4
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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. : | 71082-51-4 |
Formula : | C11H6F3NO2 |
M.W : | 241.17 |
SMILES Code : | FC(C1=CC=C2C(=C1)N=CC(=C2)C(=O)O)(F)F |
MDL No. : | MFCD11042923 |
InChI Key : | YPYGOIBPYXRZJA-UHFFFAOYSA-N |
Pubchem ID : | 33778264 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.09 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 53.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.21 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.81 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.28 |
Solubility | 0.128 mg/ml ; 0.000529 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.3 |
Solubility | 0.12 mg/ml ; 0.000497 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.97 |
Solubility | 0.026 mg/ml ; 0.000108 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) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
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 |
-5.93 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 |
0.56 |
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) |
1.48 |
* 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 |
---|---|---|
70% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 5.0h; | Example 34N-((1R)-1-{3-FLUORO-4-[(METHYLSULFONYL)AMINO]PHENYL}ETHYL)-7-(TRIFLUORO-METHYL)QUINOLINE-3-CARBOXAMIDE To a DMF (10 ml) solution of the compound of N-{4-[(1R)-1-aminoethyl]-2-fluorophenyl}methanesulfonamide hydrochloride (269 mg, 1.00 mmol), <strong>[71082-51-4]7-(trifluoromethyl)quinoline-3-carboxylic acid</strong> (241 mg, 1.00 mmol) and HBTU (455 mg, 1.20 mmol) was added triethylamine (0.7 ml, 5.00 mmol) and the mixture was stirred for 5 hours at room temperature. The same procedure as described in Example 1G was performed to give the title compound (319 mg, 70.0% yield) as a white solid.1H NMR (270 MHz, DMSO-d6) delta 1.53 (3H, d, J=6.8 Hz), 3.02 (3H, s), 5.17-5.31 (1H, m), 7.23-7.45 (3H, m), 7.94-8.02 (1H, m), 8.35-8.49 (2H, m), 9.01 (1H, s), 9.27-9.35 (1H, m), 9.42 (1H, s), 9.55 (1H, s).MS (ESI) m/z 454.19 (M-H)-, 456.20 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 2.0h; | Example 2727A) N-((1R)-1-{3,5-DIFLUORO-4-[(METHYLSULFONYL)AMINO]PHENYL}ETHYL)-7-(TRIFLUOROMETHYL)QUINOLINE-3-CARBOXAMIDE To a DMF (20 ml) solution of <strong>[71082-51-4]7-(trifluoromethyl)quinoline-3-carboxylic acid</strong> (240 mg, 1.00 mmol), the compound of Example 3D (287 mg, 1.00 mmol) and HBTU (455 mg, 1.20 mmol) was added triethylamine (0.42 ml, 3.00 mmol) and the mixture was stirred for 2 hours at room temperature. The same procedure as described in Example 10 was performed to furnish the title compound (144 mg, 30% yield) as a white solid.1H NMR (270 MHz, DMSO-d6) delta 1.53 (3H, d, J=7.3 Hz), 3.06 (3H, s), 5.17-5.31 (1H, s), 7.25-7.35 (2H, m), 7.96-8.03 (1H, m); 8.37-8.44 (1H, m), 8.46 (1H, s), 9.02-9.05 (1H, m), 9.30-9.37 (1H, m), 9.42-9.45 (1H, m), 9.51 (1H, br.s).MS (ESI) m/z 472 (M-H)-, 474 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 3.0h; | Example 4(1R)-1-{3-METHYL-4-[(METHYLSULFONYL)AMINO]PHENYL}ETHYL)-7-(TRIFLUOROMETHYL)QUINOLINE-3-CARBOXAMIDE To a DMF (10 ml) solution of the compound of Example 1D (265 mg, 1.0 mmol), <strong>[71082-51-4]7-(trifluoromethyl)quinoline-3-carboxylic acid</strong> (241 mg, 1.0 mmol) and HBTU (455 mg, 1.2 mmol) was added triethylamine (0.7 ml, 5.0 mmol) and the mixture was stirred for 3 hours at room temperature. The same procedure as described in Example 1G was performed to give the title compound (374 mg, 83% yield) as a white solid.1H NMR (DMSO-d6) delta 1.53 (3H, d, J=7.3 Hz), 2.32 (3H, s), 2.97 (3H, s), 5.13-5.28 (1H, m), 7.22-7.35 (3H, m), 7.96-8.01 (1H, m), 8.35-8.47 (2H, m), 8.99-9.05 (2H, m), 9.25-8.31 (1H, m), 9.41-9.44 (1H, m). MS (ESI) m/z 450.03 (M-H)-, 452.10 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; thionyl chloride; In dichloromethane; at 20.0℃; for 1.0h; | Example 43; N-((1R)-1-{2-FLUORO-5-METHYL-4-[(METHYLSULFONYL)AMINO]PHENYL}ETHYL)-7-(TRIFLUOROMETHYL)QUINOLINE-3-CARBOXAMIDE To a CH2Cl2 (20.0 ml) solution of <strong>[71082-51-4]7-(trifluoromethyl)quinoline-3-carboxylic acid</strong> (300 mg, 1.24 mmol), thionyl chloride (1.0 ml) and DMAP (15.2 mg, 0.124 mmol) were added and the mixture was stirred for 1 h at room temperature. Then, solvent and thionyl chloride were removed under reduced pressure to give the white solid, which was used for further reaction without purification. Then, to the pyridine (5 ml) solution of an amine (Example 13D) (352 mg, 1.24 mmol), the CH2Cl2 (20 ml) solution of the acid chloride was added and the mixture was stirred for 1 h at room temperature. The same procedure as described in Example 32 was performed to give the title compound (152 mg, 26% yield) as a white solid.1H NMR (300 MHz, CDCl3) 2.09 (3H, s), 2.26 (3H, s), 3.03 (3H, s), 5.41 (1H, t, J=7.4 Hz), 7.12 (1H, d, J=11.0 Hz), 7.39 (1H, d, J=8.8 Hz), 8.13 (1H, d, J=11.0 Hz), 8.31 (1H, d, J=8.8 Hz), 8.66 (1H, s), 9.06 (1H, s), 9.21-9.44 (3H, m).MS (ESI): m/z 470 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20.0℃; for 20.0h; | Example 53(R)-N-(1-(2-CHLORO-5-METHYL-4-(METHYLSULFONAMIDO)PHENYL)ETHYL)-7-(TRIFLUOROMETHYL)QUINOLINE-3-CARBOXAMIDE To a DMF (3 ml) solution of the compound of Example 52D (50 mg, 0.17 mmol), <strong>[71082-51-4]7-trifluoromethyl-quinoline-3-carboxylic acid</strong> (40.3 mg, 0.167 mmol), WSC (48 mg, 0.251 mmol), and HOBt hydrate (7.7 mg, 0.050 mmol) was added triethylamine (0.070 ml, 0.501 mmol) and the mixture was stirred for 20 hours at room temperature. Then the reaction was diluted with ethyl acetate-toluene (1:1, 50 ml) and washed saturated aqueous sodium bicarbonate solution, water and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo to give crude product. The crude product was purified by column chromatography on silica gel with ethyl acetate-hexane (2:1) to furnish the title compound as a white solid (39.1 mg, 48% yield).1H NMR (270 MHz, DMSO-d6) 1.50 (3H, d, J=7.2 Hz), 2.29 (3H, s), 3.03 (3H, s), 5.35-5.62 (1H, m), 7.34 (1H, s), 7.47 (1H, s), 8.13 (1H, d, J=9.2 Hz), 8.31 (1H, d, J=8.6 Hz); 8.66 (1H, s), 9.07 (1H, s), 9.23 (1H, s), 9.33 (1H, d, J=7.2 Hz), 9.46 (1H, d, J=2.6 Hz).MS (ESI) m/z 484 (M-H)-, 486 (M+H)+. |
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