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Structure of 658-89-9

Chemical Structure| 658-89-9

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Product Details of [ 658-89-9 ]

CAS No. :658-89-9
Formula : C7H7F3N2O
M.W : 192.14
SMILES Code : NC1=CC=C(OC(F)(F)F)C=C1N
MDL No. :MFCD03094278
Boiling Point : No data available
InChI Key :PIOKGAUSPFWRMD-UHFFFAOYSA-N
Pubchem ID :2773959

Safety of [ 658-89-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 658-89-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 41.93
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

61.27 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.2
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

1.83
Log Po/w (WLOGP)?

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

3.03
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.

1.03
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

0.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.61

Water Solubility

Log S (ESOL):?

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

-2.39
Solubility 0.776 mg/ml ; 0.00404 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.

-2.74
Solubility 0.352 mg/ml ; 0.00183 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

-2.31
Solubility 0.943 mg/ml ; 0.00491 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.

-6.17 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

1.0
Bioavailability Score?

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

0.55

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

1.0 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)

1.62

Application In Synthesis of [ 658-89-9 ]

* 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 [ 658-89-9 ]

[ 658-89-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 2267-23-4 ]
  • [ 658-89-9 ]
YieldReaction ConditionsOperation in experiment
98% A solution of <strong>[2267-23-4]2-nitro-4-trifluoromethoxy-phenylamine</strong> 1 (25.0 g, 0.112 mol) in EtOH (200 ml) was added to solution of stannous chloride dihydrate (82.0 g, 0.363 mol) in cone HCl (330 ml) . The resulting suspension was stirred for 0.5 h at 70-80C, cooled at 0-5C, and basified to pH=ll-12 by 40% NaOH solution, and the product extracted with ether (2x200 ml) . The organic solution was washed with water, dried over Na2Stheta4 and evaporated to dryness under reduced pressure to give the title compound as a brown oil (21.1 g, 98%).
92% With hydrogen;palladium; In ethanol; for 48h; EXAMPLE 61; 1 -(7H-Pyrro lor2,3-dlpyrimidin-4-yl)-4-(5-(trifluoromethoxy)-lH-benzordlimidazo 1-2- vDpiperidin-4-amine6 IA. 4-(trifluoromethoxy)benzene- 1 ,2-diamine 2-Nitro-4-(trifluoromethoxy)aniline (2.000 g, 9.00 mmol) and palladium (0.096 g, 0.90 mmol) were dissolved in ethanol (25 mL) and stirred under a balloon of hydrogen for 48 hours. The reaction was filtered and evaporated to dryness to afford 4-(trifluoromethoxy)- benzene-l,2-diamine (1.392 g, 7.24 mmol, 92 %) as a black oil; m/z (ESI+) (M+H)+ = ; HPLC tR = 1.53 min. IH NMR (400.132 MHz, CDC13) delta 3.41 (4H, vbrs), 6.60 - 6.58 (2H, m), 6.67 (IH, d).
86% With hydrogen;nickel; In ethanol; at 20℃; under 2585.81 Torr; <strong>[2267-23-4]2-nitro-4-trifluoromethoxy-phenylamine</strong> Compound 16a (0.5 g, 2.25 mmol) was dissolved into EtOH (30 mL) and Raney Ni (~ 0.5 g, prewashed with EtOH) was added. The mixture was shaken in a Parr shaker under H2 (50 psi) at room temperature overnight, filtered through Celite and the solvent was evaporated to dryness to provide 4-trifluoromethoxy-benzene-l,2-diamine Compound 16b (0.373 g, yield 86%) as. a red- brown semi-solid.
With hydrogen;palladium 10% on activated carbon; In methanol; under 2327.23 Torr; for 4h; To a solution of 2-Nitro-4-trifluoromethoxyaniline (4Og, 180 mmol) in methanol (250 ml), was added 10% palladium on carbon (Pd/C, 10% wt/wt, 500 mg). The suspension was shaken in a Parr bottle under 45 psi of hydrogen for 4 hours, and then filtered through celite. The filtrate was concentrated to dryness to obtain a light gray solid.
With ammonium chloride; zinc; In ethanol; water; at 60℃; for 1h; To a mixture of <strong>[2267-23-4]2-nitro-4-(trifluoromethoxy)aniline</strong> (1.17 g) and EtOH (20 mL) were added ammonium chloride (565 mg) and water (5 mL), followed by further adding zinc powder (1.73 g) at 60 C., and heating and stirring at 60 C. for 1 hour. The reaction mixture was cooled to room temperature, filtered over Celite, and washed with EtOAc. This filtrate was washed with a saturated aqueous NaHCO3 solution and brine in this order, dried over MgSO4, and then concentrated under reduced pressure to obtain 4-(trifluoromethoxy)benzene-1,2-diamine.
With ethanol; water; iron; ammonium chloride; at 70℃; for 4h; 4-(Trifluoromethoxy)-1 ,2-benzenediamine is commercially available, alternatively it can be prepared according to the following procedure. <n="45"/>To a stirred mixture of iron (2.011 g, 36.0 mmol), ammonium chloride (2.408 g, 45.0 mmol) and water (5 ml) was added dropwise a solution of 2-nitro-4- (trifluoromethoxy)aniline (commercially available from e.g. Fluorochem. Ltd., 2 g, 9.0 mmol) in ethanol (10 ml). The mixture was heated to 70 0C and stirred for 4 hours. By TLC the reaction was complete. The mixture was cooled to room temperature and filtered through celite, washing with ethanol. The filtrate was concentrated under vacuum; the residue was partitioned between dichloromethane and water. The organic phase was filtered through a hydrophobic membrane (Phase Sep) and concentrated under vacuum to give the title compound (1.51 g) as a dark brown oil. 1 H-NMR (400 MHz, CDCI3): delta 6.66 (1 H, d, J 8 Hz), 6.60-6.55 (2H, m), 3.84-2.89 (4H, m); UPLC-MS: 0.50 min, mz 193 [M+H]+.

  • 2
  • [ 916325-85-4 ]
  • [ 658-89-9 ]
  • 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (2-amino-4-trifluoromethoxy-phenyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; A mixture of S-bromo-lH-pyrazoloP^-bjpyridine-S-carboxyric acid Compound Ic (0.68 g, 1.93 mmol), Compound 16b (0.373 g, 1.93 mmol), HATU (0.73 g, 1.9 mmol) and DIPEA (1 mL, 5.8 mmol) in DMF (30 mL) was stirred at room temperature overnight. The solvent was removed under vacuum and the resulting yellow residue was mixed with AcOEt, sequentially washed with saturated aqueous NH4Cl, IM HCl, water and saturated aqueous NaHCO3, then dried over Na2SO4. The solvent was evaporated to dryness to provide 5-bromo-lH-pyrazolo[3,4-b]pyridine-3- carboxylic acid (2-amino-4-trifluoromethoxy-phenyl)-amide Compound 16c (0.67 g, 83% yield) as a yellow solid. LC-MS major peak 3.03 min, MS (ESI) m/z 416.0 (M+)/417.0 (M+H+).
  • 3
  • [ 916325-85-4 ]
  • [ 658-89-9 ]
  • 5-bromo-3-(5-trifluoromethoxy-1H-benzoimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridine [ No CAS ]
 

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