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Chemical Structure| 344-39-8 Chemical Structure| 344-39-8

Structure of 344-39-8

Chemical Structure| 344-39-8

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Product Details of [ 344-39-8 ]

CAS No. :344-39-8
Formula : C8H6F3NO3
M.W : 221.13
SMILES Code : FC(C1=CC(OC)=CC=C1[N+]([O-])=O)(F)F
MDL No. :MFCD00053611
InChI Key :RBEXRIBHQSUANC-UHFFFAOYSA-N
Pubchem ID :548517

Safety of [ 344-39-8 ]

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

Computational Chemistry of [ 344-39-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 0.0
Molar Refractivity 46.76
TPSA ?

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

55.05 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.79
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

2.54
Log Po/w (WLOGP)?

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

3.77
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.

1.68
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

0.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.11

Water Solubility

Log S (ESOL):?

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

-2.91
Solubility 0.273 mg/ml ; 0.00123 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.

-3.34
Solubility 0.1 mg/ml ; 0.000454 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

-2.8
Solubility 0.35 mg/ml ; 0.00158 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

Yes
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

Yes
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.

-5.85 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.

0.55

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

2.0 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)

1.8

Application In Synthesis of [ 344-39-8 ]

* 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 [ 344-39-8 ]

[ 344-39-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 344-39-8 ]
  • [ 53903-49-4 ]
YieldReaction ConditionsOperation in experiment
100% With nitrogen; hydrogen;palladium; In ethanol; (b) 4-Methoxy-2-(alpha,alpha,alpha-trifluoromethyl)aniline prepared by aminating 4-methoxy-2-(alpha,alpha,alpha-trifluoromethyl)nitrobenzene as follows: In a 300 ml stainless steel autoclave was placed a solution of 25.0 g (0.11 mole) of 4-methoxy-2-(alpha,alpha, alpha-trifluoromethyl)nitrobenzene in 150 ml of 95% ethanol. After flushing with nitrogen, 1.1 g of 5% palladium on carbon was added and the autoclave sealed. After flushing with nitrogen, the reactor was charged with 60 psi (413 kPa) of hydrogen and stirred. Gas uptake began immediately and the temperature was maintained between 25 C. and 30 C. by occasional cooling with an ice bath. After approximately ninety minutes, the gas uptake had ceased. The autoclave was vented, flushed with nitrogen and opened. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to afford 22 g (100% yield) of a light yellow oil which was shown to be 4-methoxy-2-(alpha,alpha,alpha-trifluoromethyl)aniline. 1 H NMR analysis indicated: (delta, CDClz) 7.82 (dd, J= 2 and 9 Hz, 1H), 7.00 (d, J=2 Hz, 1H), 6.48 (d, J=9 Hz, 1H), 3.87 (br s, 2H) and 3.60 (s, 3H). Mass spectrum analysis indicated: (m/e) 191 (M+), 176, 156, 128 and 52. It was used directly in the next step without purification.
99% With palladium 10% on activated carbon; hydrogen; In methanol; water; ethyl acetate; at 20℃; 4-methoxy-1-nitro-2-(trifluoromethyl)benzene (9.0 g, 40.7 mmol)Soluble in ethyl acetate (50 mL) and methanol (100 mL),Add 10% palladium on carbon (1.2g, 50% water),With hydrogen balloon,Stir at room temperature overnight.Filter after the reaction,The filtrate was concentrated under reduced pressure to give a yellow oil (7.7 g, 99.0%).Used directly for the next step.
With hydrogen;5%-palladium/activated carbon; In ethanol; at 20℃; for 2.5h; 4-Methoxy-2-trifluoromethylaniline; A mixture of 4-methoxy-1-nitro-2-trifluoromethyl-benzene (4.9 g, 22.2 mmol) and 5% palladium on carbon (210 mg) in EtOH (28 mL) is stirred for 2.5 h at RT, under a hydrogen atmosphere. The resulting suspension is filtered through a pad of celite. The filtrate is concentrated in vacuo to afford the title compound: ES-MS: 192.0 [M] + ; single peak at tR= 3.55 min (System 2)
With hydrazine hydrate;raney Ni; In methanol; at 20℃; Step-2:-Preperation of 4-methoxy-2-trifluoromethyl-phenylamine:-To a solution of 4-methoxy- 1 -nitro-2-trifluoromethyl-benzene (1.0 g, 4.52 mmol) in methanol (5-7 mL) was drop wise added raney Ni (cat. amount) and hydrazine hydrate (1 mL). The reaction mass was stirred at RT for 2-3 hours. The reaction mass was quenched in water and the filtrate was concentrated to afford 0.400 g of desired product. 'HNMR (DMSO- 6): delta 3.67 (s, 3H), 5.09 (s, 2H), 6.79-6.85 (m, 2H), 6.96 (d, / = 6.9 Hz, 1H).

 

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