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Chemical Structure| 71082-51-4

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Product Details of [ 71082-51-4 ]

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

Safety of [ 71082-51-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 71082-51-4 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

50.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.15
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.6
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

4.1
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.21
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.81
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.38

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.28
Solubility 0.128 mg/ml ; 0.000529 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.3
Solubility 0.12 mg/ml ; 0.000497 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.97
Solubility 0.026 mg/ml ; 0.000108 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.93 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.48

Application In Synthesis of [ 71082-51-4 ]

* 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.

  • Downstream synthetic route of [ 71082-51-4 ]

[ 71082-51-4 ] Synthesis Path-Downstream   1~11

  • 2
  • N-{4-[(1R)-1-aminoethyl]-2-fluorophenyl}methanesulfonamide hydrochloride [ No CAS ]
  • [ 71082-51-4 ]
  • [ 958328-76-2 ]
YieldReaction ConditionsOperation 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)+.
  • 3
  • [ 956901-23-8 ]
  • [ 71082-51-4 ]
  • [ 958328-53-5 ]
YieldReaction ConditionsOperation 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)+.
  • 4
  • [ 71082-51-4 ]
  • [ 958329-11-8 ]
  • 5
  • [ 886842-78-0 ]
  • [ 71082-51-4 ]
  • [ 958327-97-4 ]
YieldReaction ConditionsOperation 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)+.
  • 6
  • [ 71082-51-4 ]
  • 7-(trifluoromethyl)quinoline-3-carboxylic acid chloride [ No CAS ]
YieldReaction ConditionsOperation 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)+.
  • 7
  • [ 958332-58-6 ]
  • [ 71082-51-4 ]
  • [ 958329-43-6 ]
YieldReaction ConditionsOperation 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)+.
  • 8
  • [ 71082-51-4 ]
  • ((2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl 7-(trifluoromethyl)-quinoline-3-carboxylate [ No CAS ]
  • 9
  • [ 71082-51-4 ]
  • 3-((((2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methoxy)carbonyl)-7-trifluoromethyl-1-methylquinolin-1-ium trifluoromethanesulfonate [ No CAS ]
  • 10
  • [ 71082-51-4 ]
  • ((2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl 7-trifluoromethyl-1-methyl-1,4-dihydroquinoline-3-carboxylate [ No CAS ]
  • 11
  • [ 74124-79-1 ]
  • [ 71082-51-4 ]
  • 2,5-dioxopyrrolidin-1-yl 7-(trifluoromethyl)quinoline-3-carboxylate [ No CAS ]
 

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